Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Vascular Pharmacology
  4. Volume 23, Issue 2
  5. Article
Volume 23, Issue 2
  • ISSN: 1570-1611
  • E-ISSN: 1875-6212

Abstract

Diabetic foot ulcers (DFUs) pose a significant clinical challenge, characterized by impaired wound healing, chronic inflammation, and increased risk of infection. Neutrophils, as critical components of the innate immune response, play a pivotal role in the initial stages of wound healing, particularly during the inflammatory phase. This review explores the intricate relationship between neutrophil migration, inflammation, and the pathogenesis of DFU and drugs that can impact neutrophil production and migration. Neutrophils contribute to infection control through phagocytosis and release pro-inflammatory cytokines and reactive oxygen species, which, when dysregulated, can impede the wound healing process. Furthermore, the chronic hyperglycemic state characteristic of diabetes mellitus has been implicated in impairing neutrophil functions, including chemotaxis and oxidative burst. This compromised neutrophil response prolongs the inflammatory phase and disrupts the delicate balance required for efficient wound healing. Neutrophil extracellular traps (NETs), a unique form of neutrophil defence, have also been implicated in DFU pathogenesis, potentially exacerbating inflammation and tissue damage. Understanding the intricate interplay between neutrophil migration, dysregulated inflammatory responses, and hyperglycemia-driven impairments is essential for developing targeted therapeutic strategies for DFUs. This review sheds light on the critical role of neutrophils in DFU pathogenesis, and innovative and advanced treatment strategies for DFU, highlighting the potential for novel interventions to restore the balance between pro-inflammatory and wound healing processes, ultimately improving clinical outcomes for individuals with DFU.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cvp/10.2174/0115701611308960241014155413
2024-10-30
2025-04-21

  • From This Site

    /content/journals/cvp/10.2174/0115701611308960241014155413
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. de OliveiraS. RosowskiE.E. HuttenlocherA. Neutrophil migration in infection and wound repair: Going forward in reverse.Nat. Rev. Immunol.201616637839110.1038/nri.2016.4927231052
     [Google Scholar]
  2. MaXX. LiuQK. KuaiL. The role of neutrophils in diabetic ulcers and targeting therapeutic strategies.Int Immunopharmacol2023124Pt A11086110.1016/j.intimp.2023.110861
     [Google Scholar]
  3. GierlikowskaB. StachuraA. GierlikowskiW. DemkowU. Phagocytosis, degranulation and extracellular traps release by neutrophils: The current knowledge, pharmacological modulation and future prospects.Front. Pharmacol.20211266673210.3389/fphar.2021.66673234017259
     [Google Scholar]
  4. TetlowL.C. AdlamD.J. WoolleyD.E. Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: Associations with degenerative changes.Arthritis Rheum.200144358559411263773
     [Google Scholar]
  5. YadavS.S. SinghM.K. DwivediP. MandalR.K. UsmanK. KhattriS. PantK.K. Significance of impaired serum gelatinases activities in metabolic syndrome.Toxicol. Int.201421110711124748744
     [Google Scholar]
  6. SinghK. AgrawalN.K. GuptaS.K. MohanG. ChaturvediS. SinghK. Differential expression of matrix metalloproteinase-9 gene in wounds of type 2 Diabetes mellitus cases with susceptible -1562C>T genotypes and wound severity.Int. J. Low. Extrem. Wounds20141329410210.1177/153473461453498024861096
     [Google Scholar]
  7. LobmannR. AmbroschA. SchultzG. WaldmannK. SchiweckS. LehnertH. Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients.Diabetologia20024571011101610.1007/s00125‑002‑0868‑812136400
     [Google Scholar]
  8. Rizo-TéllezS.A. SekheriM. FilepJ.G. Myeloperoxidase: Regulation of neutrophil function and target for therapy.Antioxidants20221111230210.3390/antiox1111230236421487
     [Google Scholar]
  9. ZhangR. BrennanM.L. ShenZ. MacPhersonJ.C. SchmittD. MolendaC.E. HazenS.L. Myeloperoxidase functions as a major enzymatic catalyst for initiation of lipid peroxidation at sites of inflammation.J. Biol. Chem.200227748461164612210.1074/jbc.M20912420012359714
     [Google Scholar]
  10. SuY. RichmondA. Chemokine regulation of neutrophil infiltration of skin wounds.Adv. Wound Care (New Rochelle)201541163164010.1089/wound.2014.055926543677
     [Google Scholar]
  11. BernhardS. HugS. StratmannA.E.P. ErberM. VidoniL. KnappC.L. ThomaßB.D. FaulerM. NilssonB. Nilsson EkdahlK. FöhrK. BraunC.K. WohlgemuthL. Huber-LangM. MessererD.A.C. Interleukin 8 elicits rapid physiological changes in neutrophils that are altered by inflammatory conditions.J. Innate Immun.202113422524110.1159/00051488533857948
     [Google Scholar]
  12. Seree-aphinanC. VichitkunakornP. NavakanitworakulR. KhwannimitB. Distinguishing sepsis from infection by neutrophil dysfunction: A promising role of CXCR2 surface level.Front. Immunol.20201160869610.3389/fimmu.2020.60869633424860
     [Google Scholar]
  13. TengT.S. JiA. JiX.Y. LiY.Z. Neutrophils and immunity: From bactericidal action to being conquered.J. Immunol. Res.2017201711410.1155/2017/967160428299345
     [Google Scholar]
  14. RosalesC. Neutrophil: A cell with many roles in inflammation or several cell types?Front. Physiol.2018911310.3389/fphys.2018.0011329515456
     [Google Scholar]
  15. LuP. TakaiK. WeaverV.M. WerbZ. Extracellular matrix degradation and remodeling in development and disease.Cold Spring Harb. Perspect. Biol.2011312a00505810.1101/cshperspect.a00505821917992
     [Google Scholar]
  16. WilgusT.A. RoyS. McDanielJ.C. Neutrophils and wound repair: Positive actions and negative reactions.Adv. Wound Care (New Rochelle)20132737938810.1089/wound.2012.038324527354
     [Google Scholar]
  17. AdroverJ.M. Nicolás-ÁvilaJ.A. HidalgoA. Aging: A temporal dimension for neutrophils.Trends Immunol.201637533434510.1016/j.it.2016.03.00527083489
     [Google Scholar]
  18. HiranoY. AzizM. WangP. Role of reverse transendothelial migration of neutrophils in inflammation.Biol. Chem.2016397649750610.1515/hsz‑2015‑030926872312
     [Google Scholar]
  19. JinH. AzizM. OdeY. WangP. CIRP induces neutrophil reverse transendothelial migration in sepsis.Shock201951554855610.1097/SHK.000000000000125730148763
     [Google Scholar]
  20. RobertsonA.L. HolmesG.R. BojarczukA.N. BurgonJ. LoynesC.A. ChimenM. SawtellA.K. HamzaB. WillsonJ. WalmsleyS.R. AndersonS.R. ColesM.C. FarrowS.N. SolariR. JonesS. PrinceL.R. IrimiaD. RaingerG.E. KadirkamanathanV. WhyteM.K.B. RenshawS.A. A zebrafish compound screen reveals modulation of neutrophil reverse migration as an anti-inflammatory mechanism.Sci. Transl. Med.20146225225ra2910.1126/scitranslmed.300767224574340
     [Google Scholar]
  21. VorobjevaN.V. ChernyakB.V. NETosis: Molecular mechanisms, role in physiology and pathology.Biochemistry (Mosc.)202085101178119010.1134/S000629792010006533202203
     [Google Scholar]
  22. SabbatiniM. MagnelliV. RenòF. NETosis in wound healing: When enough is enough.Cells202110349410.3390/cells1003049433668924
     [Google Scholar]
  23. WongS.L. DemersM. MartinodK. GallantM. WangY. GoldfineA.B. KahnC.R. WagnerD.D. Diabetes primes neutrophils to undergo NETosis, which impairs wound healing.Nat. Med.201521781581910.1038/nm.388726076037
     [Google Scholar]
  24. DoweyR. IqbalA. HellerS.R. SabroeI. PrinceL.R. A bittersweet response to infection in diabetes; targeting neutrophils to modify inflammation and improve host immunity.Front. Immunol.20211267877110.3389/fimmu.2021.67877134149714
     [Google Scholar]
  25. CollierA. JacksonM. BellD. PatrickA.W. MatthewsD.M. YoungR.J. ClarkeB.F. DawesJ. Neutrophil activation detected by increased neutrophil elastase activity in type 1 (insulin-dependent) diabetes mellitus.Diabetes Res.19891031351382805587
     [Google Scholar]
  26. JacksonM.H. CollierA. NicollJ.J. MuirA.L. DawesJ. ClarkeB.F. BellD. Neutrophil count and activation in vascular disease.Scott. Med. J.1992372414310.1177/0036933092037002051609264
     [Google Scholar]
  27. HarsunenM. PuffR. D’OrlandoO. GiannopoulouE. LachmannL. BeyerleinA. von MeyerA. ZieglerA.G. Reduced blood leukocyte and neutrophil numbers in the pathogenesis of type 1 diabetes.Horm. Metab. Res.201345646747010.1055/s‑0032‑133122623322517
     [Google Scholar]
  28. WangY. XiaoY. ZhongL. YeD. ZhangJ. TuY. BornsteinS.R. ZhouZ. LamK.S.L. XuA. Increased neutrophil elastase and proteinase 3 and augmented NETosis are closely associated with β-cell autoimmunity in patients with type 1 diabetes.Diabetes201463124239424810.2337/db14‑048025092677
     [Google Scholar]
  29. SprostonN.R. AshworthJ.J. Role of C-reactive protein at sites of inflammation and infection.Front. Immunol.2018975410.3389/fimmu.2018.0075429706967
     [Google Scholar]
  30. DubeyM. SinghA.K. AwasthiD. NagarkotiS. KumarS. AliW. ChandraT. KumarV. BarthwalM.K. JagaveluK. Sánchez-GómezF.J. LamasS. DikshitM. L-Plastin S-glutathionylation promotes reduced binding to β-actin and affects neutrophil functions.Free Radic. Biol. Med.20158611510.1016/j.freeradbiomed.2015.04.00825881549
     [Google Scholar]
  31. MenegazzoL. CiciliotS. PoncinaN. MazzucatoM. PersanoM. BonoraB. AlbieroM. Vigili de KreutzenbergS. AvogaroA. FadiniG.P. NETosis is induced by high glucose and associated with type 2 diabetes.Acta Diabetol.201552349750310.1007/s00592‑014‑0676‑x25387570
     [Google Scholar]
  32. CarestiaA. FrechtelG. CerroneG. LinariM.A. GonzalezC.D. CasaisP. SchattnerM. NETosis before and after hyperglycemic control in type 2 Diabetes mellitus patients.PLoS One20161112e016864710.1371/journal.pone.016864728005949
     [Google Scholar]
  33. Rodríguez-EspinosaO. Rojas-EspinosaO. Moreno-AltamiranoM.M.B. López-VillegasE.O. Sánchez-GarcíaF.J. Metabolic requirements for neutrophil extracellular traps formation.Immunology2015145221322410.1111/imm.1243725545227
     [Google Scholar]
  34. JoshiM.B. LadA. Bharath PrasadA.S. BalakrishnanA. RamachandraL. SatyamoorthyK. High glucose modulates IL‐6 mediated immune homeostasis through impeding neutrophil extracellular trap formation.FEBS Lett.2013587142241224610.1016/j.febslet.2013.05.05323735697
     [Google Scholar]
  35. HuangJ. XiaoY. ZhengP. ZhouW. WangY. HuangG. XuA. ZhouZ. Distinct neutrophil counts and functions in newly diagnosed type 1 diabetes, latent autoimmune diabetes in adults, and type 2 diabetes.Diabetes Metab. Res. Rev.2019351e306410.1002/dmrr.306430123986
     [Google Scholar]
  36. TrevelinS.C. CarlosD. BerettaM. da SilvaJ.S. CunhaF.Q. Diabetes Mellitus and Sepsis.Shock201747327628710.1097/SHK.000000000000077827787406
     [Google Scholar]
  37. ÖzsoyN. BostancıH. AyvalıC. The investigation of the ultrastructural neutrophil changes in alloxan‐induced diabetes in rats: Response to a chemotactic challenge.Cell Biochem. Funct.2004222818710.1002/cbf.105915027096
     [Google Scholar]
  38. InsuelaD. CoutinhoD. MartinsM. FerreroM. CarvalhoV. Neutrophil function impairment is a host susceptibility factor to bacterial infection in Diabetes.Cells of the Immune SystemInTech Open201910.5772/intechopen.86600
     [Google Scholar]
  39. VeenstraM. RansohoffR.M. Chemokine receptor CXCR2: Physiology regulator and neuroinflammation controller?J. Neuroimmunol.20122461-21910.1016/j.jneuroim.2012.02.01622445294
     [Google Scholar]
  40. EverettE. MathioudakisN. Update on management of diabetic foot ulcers.Ann. N. Y. Acad. Sci.20181411115316510.1111/nyas.1356929377202
     [Google Scholar]
  41. TuttolomondoA. MaidaC. PintoA. Diabetic foot syndrome: Immune-inflammatory features as possible cardiovascular markers in diabetes.World J. Orthop.201561627610.5312/wjo.v6.i1.6225621212
     [Google Scholar]
  42. BurgessJ.L. WyantW.A. Abdo AbujamraB. KirsnerR.S. JozicI. Diabetic wound-healing science.Medicina (Kaunas)20215710107210.3390/medicina5710107234684109
     [Google Scholar]
  43. XuF. ZhangC. GravesD.T. Abnormal cell responses and role of TNF-α in impaired diabetic wound healing.BioMed Res. Int.201320131910.1155/2013/75480223484152
     [Google Scholar]
  44. SathvikM. VuppuluriK. DulipalaP. The association of the neutrophil-lymphocyte ratio with the outcome of diabetic foot ulcer.Cureus2023151e3389110.7759/cureus.3389136819314
     [Google Scholar]
  45. LiX.H. GuanL.Y. LinH.Y. WangS.H. CaoY.Q. JiangX.Y. WangY.B. Fibrinogen: A marker in predicting diabetic foot ulcer severity.J. Diabetes Res.201620161510.1155/2016/235832128044140
     [Google Scholar]
  46. StegengaM.E. van der CrabbenS.N. BlümerR.M.E. LeviM. MeijersJ.C.M. SerlieM.J. TanckM.W.T. SauerweinH.P. van der PollT. Hyperglycemia enhances coagulation and reduces neutrophil degranulation, whereas hyperinsulinemia inhibits fibrinolysis during human endotoxemia.Blood20081121828910.1182/blood‑2007‑11‑12172318316629
     [Google Scholar]
  47. RoyR. ZayasJ. SinghS.K. DelgadoK. WoodS.J. MohamedM.F. FraustoD.M. AlbalawiY.A. PriceT.P. EstupinianR. GiuriniE.F. KuzelT.M. ZlozaA. ReiserJ. ShafikhaniS.H. Overriding impaired FPR chemotaxis signaling in diabetic neutrophil stimulates infection control in murine diabetic wound.eLife202211e7207110.7554/eLife.7207135112667
     [Google Scholar]
  48. JavidA. ZlotnikovN. PětrošováH. TangT.T. ZhangY. BansalA.K. EbadyR. ParikhM. AhmedM. SunC. NewbiggingS. KimY.R. Santana SosaM. GlogauerM. MoriartyT.J. Hyperglycemia impairs neutrophil-mediated bacterial clearance in mice infected with the lyme disease pathogen.PLoS One2016116e015801910.1371/journal.pone.015801927340827
     [Google Scholar]
  49. AsmatU. AbadK. IsmailK. Diabetes mellitus and oxidative stress: A concise review.Saudi Pharm. J.201624554755310.1016/j.jsps.2015.03.01327752226
     [Google Scholar]
  50. NjeimR. AzarW.S. FaresA.H. AzarS.T. Kfoury KassoufH. EidA.A. NETosis contributes to the pathogenesis of diabetes and its complications.J. Mol. Endocrinol.2020654R65R7610.1530/JME‑20‑012833048064
     [Google Scholar]
  51. FadiniG.P. MenegazzoL. RigatoM. ScattoliniV. PoncinaN. BruttocaoA. CiciliotS. MammanoF. CiubotaruC.D. BroccoE. MarescottiM.C. CappellariR. ArrigoniG. MillioniR. Vigili de KreutzenbergS. AlbieroM. AvogaroA. NETosis delays diabetic wound healing in mice and humans.Diabetes20166541061107110.2337/db15‑086326740598
     [Google Scholar]
  52. BerbudiA. RahmadikaN. TjahjadiA.I. RuslamiR. Type 2 Diabetes and its impact on the immune system.Curr. Diabetes Rev.202016544244910.2174/18756417MTAxgODQqy31657690
     [Google Scholar]
  53. MortazE. AlipoorS.D. AdcockI.M. MumbyS. KoendermanL. Update on neutrophil function in severe inflammation.Front. Immunol.20189217110.3389/fimmu.2018.0217130356867
     [Google Scholar]
  54. FiorentinoT. PriolettaA. ZuoP. FolliF. Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases.Curr. Pharm. Des.201319325695570310.2174/138161281131932000523448484
     [Google Scholar]
  55. GengK. MaX. JiangZ. HuangW. GaoC. PuY. LuoL. XuY. XuY. Innate immunity in diabetic wound healing: Focus on the mastermind hidden in chronic inflammatory.Front. Pharmacol.20211265394010.3389/fphar.2021.65394033967796
     [Google Scholar]
  56. TracyL.E. MinasianR.A. CatersonE.J. Extracellular matrix and dermal fibroblast function in the healing wound.Adv. Wound Care (New Rochelle)20165311913610.1089/wound.2014.056126989578
     [Google Scholar]
  57. BrubakerA.L. RendonJ.L. RamirezL. ChoudhryM.A. KovacsE.J. Reduced neutrophil chemotaxis and infiltration contributes to delayed resolution of cutaneous wound infection with advanced age.J. Immunol.201319041746175710.4049/jimmunol.120121323319733
     [Google Scholar]
  58. GuoS. DiPietroL.A. Factors affecting wound healing.J. Dent. Res.201089321922910.1177/002203450935912520139336
     [Google Scholar]
  59. Shaikh-KaderA. HoureldN.N. RajendranN.K. AbrahamseH. The link between advanced glycation end products and apoptosis in delayed wound healing.Cell Biochem. Funct.201937643244210.1002/cbf.342431318458
     [Google Scholar]
  60. OchoaO. TorresF.M. ShiremanP.K. Chemokines and diabetic wound healing.Vascular200715635035510.2310/6670.2007.0005618053419
     [Google Scholar]
  61. RidiandriesA. TanJ.T.M. BursillC.A. The role of chemokines in wound healing.Int. J. Mol. Sci.20181910321710.3390/ijms1910321730340330
     [Google Scholar]
  62. LandénN.X. LiD. StåhleM. Transition from inflammation to proliferation: A critical step during wound healing.Cell. Mol. Life Sci.201673203861388510.1007/s00018‑016‑2268‑027180275
     [Google Scholar]
  63. SpillerF. CarlosD. SoutoF.O. de FreitasA. SoaresF.S. VieiraS.M. PaulaF.J.A. Alves-FilhoJ.C. CunhaF.Q. α1-Acid glycoprotein decreases neutrophil migration and increases susceptibility to sepsis in diabetic mice.Diabetes20126161584159110.2337/db11‑082522415874
     [Google Scholar]
  64. ZhaoB. LiM. SuY. ShanS. QianW. ZhuD. LiuX. ZhangZ. Role of transcription factor FOXM1 in diabetes and its complications (Review).Int. J. Mol. Med.202352510110.3892/ijmm.2023.530437681487
     [Google Scholar]
  65. SawayaA.P. StoneR.C. MehdizadehS. PastarI. WorrellS. BalukoffN.C. KaplanM.J. Tomic-CanicM. MorassoM.I. FOXM1 network in association with TREM1 suppression regulates NET formation in diabetic foot ulcers.EMBO Rep.2022238e5455810.15252/embr.20215455835856334
     [Google Scholar]
  66. MorrisR. KershawN.J. BabonJ.J. The molecular details of cytokine signaling via the JAK/STAT pathway.Protein Sci.201827121984200910.1002/pro.351930267440
     [Google Scholar]
  67. LeeE.G. Luckett-ChastainL.R. CalhounK.N. FrempahB. BastianA. GallucciR.M. Interleukin 6 Function in the skin and isolated keratinocytes is modulated by hyperglycemia.J. Immunol. Res.201920191910.1155/2019/508784731073533
     [Google Scholar]
  68. HillmerE.J. ZhangH. LiH.S. WatowichS.S. STAT3 signaling in immunity.Cytokine Growth Factor Rev.20163111510.1016/j.cytogfr.2016.05.00127185365
     [Google Scholar]
  69. ZhuB.M. IshidaY. RobinsonG.W. Pacher-ZavisinM. YoshimuraA. MurphyP.M. HennighausenL. SOCS3 negatively regulates the gp130-STAT3 pathway in mouse skin wound healing.J. Invest. Dermatol.200812871821182910.1038/sj.jid.570122418185532
     [Google Scholar]
  70. Hosseini MansoubN. The role of keratinocyte function on the defected diabetic wound healing.Int. J. Burns Trauma202111643044135111377
     [Google Scholar]
  71. LinkeA. GorenI. BöslM.R. PfeilschifterJ. FrankS. Epithelial overexpression of SOCS-3 in transgenic mice exacerbates wound inflammation in the presence of elevated TGF-beta1.J. Invest. Dermatol.2010130386687510.1038/jid.2009.34519924141
     [Google Scholar]
  72. SawayaA.P. StoneR.C. BrooksS.R. PastarI. JozicI. HasneenK. O’NeillK. MehdizadehS. HeadC.R. StrboN. MorassoM.I. Tomic-CanicM. Deregulated immune cell recruitment orchestrated by FOXM1 impairs human diabetic wound healing.Nat. Commun.2020111467810.1038/s41467‑020‑18276‑032938916
     [Google Scholar]
  73. JohnsonB.Z. StevensonA.W. PrêleC.M. FearM.W. WoodF.M. The role of IL-6 in skin fibrosis and cutaneous wound healing.Biomedicines20208510110.3390/biomedicines805010132365896
     [Google Scholar]
  74. BuonaceraA. StancanelliB. ColaciM. MalatinoL. Neutrophil to lymphocyte ratio: An emerging marker of the relationships between the immune system and diseases.Int. J. Mol. Sci.2022237363610.3390/ijms2307363635408994
     [Google Scholar]
  75. KahramanC. YumunG. KahramanNK. Neutrophil-to-lymphocyte ratio in diabetes mellitus patients with and without diabetic foot ulcer.EJMS20141181310.12973/ejms.2014.102p
     [Google Scholar]
  76. VatankhahN. JahangiriY. LandryG.J. McLaffertyR.B. AlkayedN.J. MonetaG.L. AzarbalA.F. Predictive value of neutrophil-to-lymphocyte ratio in diabetic wound healing.J. Vasc. Surg.201765247848310.1016/j.jvs.2016.08.10827887858
     [Google Scholar]
  77. ZhangK. DingS. LyuX. TanQ. WangZ. Correlation between the platelet‐to‐lymphocyte ratio and diabetic foot ulcer in patients with type 2 diabetes mellitus.J. Clin. Lab. Anal.2021354e2371910.1002/jcla.2371933507619
     [Google Scholar]
  78. SerbanD. PapanasN. DascaluAM. Significance of neutrophil to lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in Diabetic foot ulcer and potential new therapeutic targets.Int J Low Extrem Wounds202423220521610.1177/15347346211057742.34791913
     [Google Scholar]
  79. AtakB. AktasG. DumanTT. ErkusE. KocakMZ. SavliH. Diabetes control could through platelet-to-lymphocyte ratio in hemograms.Rev Assoc Med Bras (1992)2019651384210.1590/1806‑9282.65.1.38
     [Google Scholar]
  80. MineokaY. IshiiM. HashimotoY. YamashitaA. NakamuraN. FukuiM. Platelet to lymphocyte ratio correlates with diabetic foot risk and foot ulcer in patients with type 2 diabetes.Endocr. J.2019661090591310.1507/endocrj.EJ18‑047731217392
     [Google Scholar]
  81. ChenW. ChenK. XuZ. HuY. LiuY. LiuW. HuX. YeT. HongJ. ZhuH. ShenF. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio predict mortality in patients with diabetic foot ulcers undergoing amputations.Diabetes Metab. Syndr. Obes.20211482182910.2147/DMSO.S28458333658817
     [Google Scholar]
  82. PanopoulosA.D. WatowichS.S. Granulocyte colony-stimulating factor: Molecular mechanisms of action during steady state and ‘emergency’ hematopoiesis.Cytokine200842327728810.1016/j.cyto.2008.03.00218400509
     [Google Scholar]
  83. LinkH. Current state and future opportunities in granulocyte colony-stimulating factor (G-CSF).Support. Care Cancer20223097067707710.1007/s00520‑022‑07103‑535739328
     [Google Scholar]
  84. AnderliniP. PrzepiorkaD. SeongD. MillerP. SundbergJ. LichtigerB. NorfleetF. ChanK.W. ChamplinR. KörblingM. Clinical toxicity and laboratory effects of granulocyte-colony-stimulating factor (filgrastim) mobilization and blood stem cell apheresis from normal donors, and analysis of charges for the procedures.Transfusion199636759059510.1046/j.1537‑2995.1996.36796323057.x8701453
     [Google Scholar]
  85. EdmondsM. GoughA. SoloveraJ. StandaertB. Filgrastim in the treatment of infected diabetic foot ulcers.Clin. Drug Investig.199917427528610.2165/00044011‑199917040‑00003
     [Google Scholar]
  86. RastogiS. KalaiselvanV. AliS. AhmadA. GuruS.A. SarwatM. Efficacy and safety of filgrastim and its biosimilars to prevent febrile neutropenia in cancer patients: A prospective study and meta-analysis.Biology (Basel)20211010106910.3390/biology1010106934681169
     [Google Scholar]
  87. BaldoB.A. Side effects of cytokines approved for therapy.Drug Saf.2014371192194310.1007/s40264‑014‑0226‑z25270293
     [Google Scholar]
  88. WestphalenD. Neulasta (pegfilgrastim).Available from: https://www.medicalnewstoday.com/articles/neulasta#about.
  89. AaproM. BocciaR. LeonardR. CampsC. CamponeM. ChoquetS. DanovaM. GlaspyJ. HusI. LinkH. SliwaT. TeschH. ValeroV. Refining the role of pegfilgrastim (a long-acting G-CSF) for prevention of chemotherapy-induced febrile neutropenia: Consensus guidance recommendations.Support. Care Cancer201725113295330410.1007/s00520‑017‑3842‑128842778
     [Google Scholar]
  90. InnocentiR. RigacciL. RestelliU. ScappiniB. GianfaldoniG. FanciR. MannelliF. ScolariF. CroceD. BonizzoniE. PerroneT. BosiA. Lenograstim and filgrastim in the febrile neutropenia prophylaxis of hospitalized patients: Efficacy and cost of the prophylaxis in a retrospective survey.J. Blood Med.201810212710.2147/JBM.S18678630643475
     [Google Scholar]
  91. MartinoM. ConsoleG. DattolaA. CalleaI. MessinaG. MoscatoT. MassaraE. IrreraG. FedeleR. GervasiA. BresolinG. IacopinoP. Short and long-term safety of lenograstim administration in healthy peripheral haematopoietic progenitor cell donors: A single centre experience.Bone Marrow Transplant.200944316316810.1038/bmt.2008.44019182833
     [Google Scholar]
  92. de LallaF. PellizzerG. StrazzaboscoM. MartiniZ. Du JardinG. LoraL. FabrisP. BenedettiP. ErleG. Randomized prospective controlled trial of recombinant granulocyte colony-stimulating factor as adjunctive therapy for limb-threatening diabetic foot infection.Antimicrob. Agents Chemother.20014541094109810.1128/AAC.45.4.1094‑1098.200111257020
     [Google Scholar]
  93. HoggattJ. TateT.A. PelusL.M. Role of lipegfilgrastim in the management of chemotherapy-induced neutropenia.Int. J. Nanomedicine2015102647265225878498
     [Google Scholar]
  94. GuarigliaR. MartorelliM.C. LeroseR. TelescaD. MilellaM.R. MustoP. Lipegfilgrastim in the management of chemotherapy-induced neutropenia of cancer patients.Biologics2016101826858523
     [Google Scholar]
  95. EttlT. SchulzD. BauerR. The renaissance of cyclin dependent kinase inhibitors.Cancers (Basel)202214229310.3390/cancers1402029335053461
     [Google Scholar]
  96. ChenR. ChenY. XiongP. ZhelevaD. BlakeD. KeatingM.J. WierdaW.G. PlunkettW. Cyclin-dependent kinase inhibitor fadraciclib (CYC065) depletes anti-apoptotic protein and synergizes with venetoclax in primary chronic lymphocytic leukemia cells.Leukemia20223661596160810.1038/s41375‑022‑01553‑w35383271
     [Google Scholar]
  97. RaedlerL.A. Zarxio (Filgrastim-sndz): First biosimilar approved in the United States.Am Health Drug Benefits20169150427668063
     [Google Scholar]
  98. OpfermannP. DerhaschnigU. FelliA. WenischJ. SanterD. ZuckermannA. DworschakM. JilmaB. SteinlechnerB. A pilot study on reparixin, a CXCR1/2 antagonist, to assess safety and efficacy in attenuating ischaemia–reperfusion injury and inflammation after on-pump coronary artery bypass graft surgery.Clin. Exp. Immunol.2015180113114210.1111/cei.1248825402332
     [Google Scholar]
  99. JoA. KimD.W. Neutrophil extracellular traps in airway diseases: Pathological roles and therapeutic implications.Int. J. Mol. Sci.2023245503410.3390/ijms2405503436902466
     [Google Scholar]
  100. SitaruS. BudkeA. BertiniR. SperandioM. Therapeutic inhibition of CXCR1/2: Where do we stand?Intern. Emerg. Med.20231861647166410.1007/s11739‑023‑03309‑537249756
     [Google Scholar]
  101. GoldsteinL.J. PerezR.P. YardleyD. HanL.K. ReubenJ.M. GaoH. McCannaS. ButlerB. RuffiniP.A. LiuY. RosatoR.R. ChangJ.C. A window-of-opportunity trial of the CXCR1/2 inhibitor reparixin in operable HER-2-negative breast cancer.Breast Cancer Res.2020221410.1186/s13058‑019‑1243‑831924241
     [Google Scholar]
  102. YangS. FengY. ChenL. WangZ. ChenJ. NiQ. GuoX. ZhangL. XueG. Disulfiram accelerates diabetic foot ulcer healing by blocking NET formation via suppressing the NLRP3/Caspase-1/GSDMD pathway.Transl. Res.202325411512710.1016/j.trsl.2022.10.00836336332
     [Google Scholar]
  103. TerposE. KleberM. EngelhardtM. ZweegmanS. GayF. KastritisE. van de DonkN.W.C.J. BrunoB. SezerO. BroijlA. BringhenS. BeksacM. LaroccaA. HajekR. MustoP. JohnsenH.E. MorabitoF. LudwigH. CavoM. EinseleH. SonneveldP. DimopoulosM.A. PalumboA. European myeloma network guidelines for the management of multiple myeloma-related complications.Haematologica2015100101254126610.3324/haematol.2014.11717626432383
     [Google Scholar]
  104. OkouchiM. OkayamaN. OmiH. ImaedaK. FukutomiT. NakamuraA. ItohM. The antidiabetic agent, gliclazide, reduces high insulin–enhanced neutrophil-transendothelial migration through direct effects on the endothelium.Diabetes Metab. Res. Rev.200420323223810.1002/dmrr.44415133755
     [Google Scholar]
  105. EzhilarasuH Biocompatible aloe vera and tetracycline hydrochloride loaded hybrid nanofibrous scaffolds for skin tissue engineering.Int J Mol Sci201920(20)10.3390/ijms2020517431635374
     [Google Scholar]
  106. MauricioMD Nanoparticles in medicine: A focus on vascular oxidative stress.Oxid Med Cell Longev20182018623148210.1155/2018/623148230356429
     [Google Scholar]
  107. HeJ Anti-oxidant electroactive and antibacterial nanofibrous wound dressings based on poly(ε-caprolactone)/quaternized chitosan-graft-polyaniline for full-thickness skin wound healing.Chemical Engineering Journal202038510.1016/j.cej.2019.123464
     [Google Scholar]
  108. ZhangHM Mesenchymal stem cells-based drug delivery systems for diabetic foot ulcer: A review.World J Diabetes202314111585160210.4239/wjd.v14.i11.158538077806
     [Google Scholar]
  109. ChenS Mesenchymal stem cell-laden anti-inflammatory hydrogel enhances diabetic wound healing.Sci Rep201551810410.1038/srep1810426643550
     [Google Scholar]
  110. DongY Acceleration of diabetic wound regeneration using an in situ-formed stem-cell-based skin substitute.Adv Healthc Mater2018717e180043210.1002/adhm.20180043230004192
     [Google Scholar]
  111. LeiZ Bone marrow-derived mesenchymal stem cells laden novel thermo-sensitive hydrogel for the management of severe skin wound healing.Mater Sci Eng C Mater Biol Appl20189015916710.1016/j.msec.2018.04.04529853078
     [Google Scholar]
  112. DaiC S.Shih A.Khachemoune Skin substitutes for acute and chronic wound healing: An updated review.J Dermatolog Treat202031663964810.1080/09546634.2018.153044330265595
     [Google Scholar]
  113. TauscheAK An autologous epidermal equivalent tissue-engineered from follicular outer root sheath keratinocytes is as effective as split-thickness skin autograft in recalcitrant vascular leg ulcers.Wound Repair Regen20031142485210.1046/j.1524‑475x.2003.11403.x12846911
     [Google Scholar]
  114. ChandlerLA Wound conforming matrix containing purified homogenate of dermal collagen promotes healing of diabetic neuropathic foot ulcers: Comparative analysis versus standard of care.Adv Wound Care (New Rochelle)202092616710.1089/wound.2019.102431903299
     [Google Scholar]
  115. HartCE A.Loewen-Rodriguez J.Lessem Dermagraft: Use in the treatment of chronic wounds.Adv Wound Care (New Rochelle)20121313814110.1089/wound.2011.028224527294
     [Google Scholar]
  116. MajumderS T.Monda lMJ Deen Wearable sensors for remote health monitoring.Sensors (Basel)201717110.3390/s1701013028085085
     [Google Scholar]
  117. BeachC Monitoring of dynamic plantar foot temperatures in diabetes with personalised 3D-printed wearables.Sensors (Basel)202121510.3390/s2105171733801346
     [Google Scholar]
  118. ChhikaraK Progress of additive manufacturing in fabrication of foot orthoses for diabetic patients: A review.Annals of 3D Printed Medicine2022810.1016/j.stlm.2022.100085
     [Google Scholar]
  119. MancusoM 3D-printed insoles for people with type 2 diabetes: An Italian, ambulatory case report on the innovative care model diabetology20234333935510.3390/diabetology4030029
     [Google Scholar]
  120. AnggoroPw Computer-aided reverse engineering system in the design and production of orthotic insole shoes for patients with diabetes.Cogent Engineering20185110.1080/23311916.2018.1470916
     [Google Scholar]
  121. TelferS Virtually optimized insoles for offloading the diabetic foot: A randomized crossover study.J Biomechanics20176015716110.1016/j.jbiomech.2017.06.02828687150
     [Google Scholar]
/content/journals/cvp/10.2174/0115701611308960241014155413
Loading
Neutrophil Migration is a Crucial Factor in Wound Healing and the Pathogenesis of Diabetic Foot Ulcers: Insights into Pharmacological Interventions
Curr. Vasc. Pharmacol. 23, 98 (2025); https://doi.org/10.2174/0115701611308960241014155413
/content/journals/cvp/10.2174/0115701611308960241014155413
/content/journals/cvp/10.2174/0115701611308960241014155413
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Diabetes mellitus; diabetic foot ulcers; inflammation; neutrophil; oxidative stress, infection

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test