Cited by 616Wound Healing and TreatmentsNeutrophil, Myeloperoxidase and Oxidative MechanismsProtease and Inhibitor Mechanisms

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Neutrophils and Wound Repair: Positive Actions and Negative Reactions

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Wilgus, Traci A., Roy, Sashwati, McDaniel, Jodi C.·2013·Advances in Wound Care

DOI 10.1089/wound.2012.0383PMC PMC3763227

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Abstract

SIGNIFICANCE: Neutrophils are one of the most abundant cells of the immune system and they are extremely active during the repair of cutaneous wounds. In general, the antimicrobial activity of neutrophils is effective and allows these cells to carry out their primary function of preventing wounds from becoming infected. RECENT ADVANCES: It is now known that in addition to sterilizing the wound, the weapons used by neutrophils to kill potential pathogens can also cause significant tissue damage to the host. This additional damage can lead to delayed healing and excessive scar formation. CRITICAL ISSUES: Much of the host damage caused by neutrophils results from the activity of proteases secreted by these cells. The clinical significance of this problem is highlighted by numerous studies showing that high levels of neutrophil-derived proteases are associated with chronic, non-healing wounds. FUTURE DIRECTIONS: Studies are currently being performed to evaluate new ways of counteracting protease activity in chronic wounds. Additional studies will have to be carried out to determine whether neutralizing neutrophil proteases can improve the healing of chronic wounds without sacrificing the ability of neutrophils to eliminate pathogens and risking infection.

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Of Mice and Not Men: Differences between Mouse and Human Immunology
Mestas, J., & Hughes, C. C. W. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.5.2731 · Cited by 3,822
Neutrophils and immunity: challenges and opportunities
Nathan, C. (2006) · Nature reviews. Immunology · doi:10.1038/nri1785 · Cited by 2,971
Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators
Serhan, C. N., Chiang, N., & Van Dyke, T. E. (2008) · Nature Reviews Immunology · doi:10.1038/nri2294 · Cited by 2,932
Matrix metalloproteinases as modulators of inflammation and innate immunity
Parks, W. C., Wilson, C. L., & López-Boado, Y. S. (2004) · Nature Reviews Immunology · doi:10.1038/nri1418 · Cited by 1,929
Neutrophils: Molecules, Functions and Pathophysiological Aspects
Witko‐Sarsat, V., Rieu, P., Descamps‐Latscha, B., Lesavre, P., & Halbwachs‐Mecarelli, L. (2000) · Laboratory Investigation · doi:10.1038/labinvest.3780067 · Cited by 1,165
Neutrophil granules and secretory vesicles in inflammation
Faurschou, M., & Borregaard, N. (2003) · Microbes and Infection · doi:10.1016/j.micinf.2003.09.008 · Cited by 1,162
Neutrophil granules: a library of innate immunity proteins
Borregaard, N., Sørensen, O. E., & Theilgaard‐Mönch, K. (2007) · Trends in Immunology · doi:10.1016/j.it.2007.06.002 · Cited by 735
Wound Fluid from Chronic Leg Ulcers Contains Elevated Levels of Metalloproteinases MMP-2 and MMP-9
Wysocki, A. B., Staiano-Coico, L., & Grinnell, F. (1993) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12359590 · Cited by 732
Macrophage Dysfunction Impairs Resolution of Inflammation in the Wounds of Diabetic Mice
Khanna, S., Biswas, S., Shang, Y., Collard, E., Azad, A., Kauh, C., Bhasker, V., Gordillo, G. M., Sen, C. K., & Roy, S. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009539 · Cited by 694
Self-citation
Accelerated wound closure in neutrophil-depleted mice
Dovi, J. V., He, L.-K., & DiPietro, L. A. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0802406 · Cited by 525
Wound Healing in the PU.1 Null Mouse—Tissue Repair Is Not Dependent on Inflammatory Cells
Martin, P. B., D'Souza, D., Martin, J. S., Grose, R. P., Cooper, L., Maki, R. A., & McKercher, S. R. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00396-8 · Cited by 490
Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing
Ashcroft, G. S., Lei, K.-J., Jin, W., Longenecker, G., Kulkarni, A. B., Greenwell‐Wild, T., Hale‐Donze, H., McGrady, G., Song, X.-Y., & Wahl, S. M. (2000) · Nature Medicine · doi:10.1038/80489 · Cited by 416
The neutrophilic leukocyte in wound repair
Simpson, D. M., & Ross, R. (1972) · Journal of Clinical Investigation · doi:10.1172/jci107007 · Cited by 394
Immunodeficiency Diseases Caused by Defects in Phagocytes
Lekstrom-Himes, J. A., & Gallin, J. I. (2000) · New England Journal of Medicine · doi:10.1056/nejm200012073432307 · Cited by 388
MMP-8 Is the Predominant Collagenase in Healing Wounds and Nonhealing Ulcers
Nwomeh, B. C., Liang, H.-X., Cohen, I. K., & Yager, D. R. (1999) · Journal of Surgical Research · doi:10.1006/jsre.1998.5495 · Cited by 357
Activation of progelatinase A (MMP‐2) by neutrophil elastase, cathepsin G, and proteinase‐3: A role for inflammatory cells in tumor invasion and angiogenesis
Shamamian, P. E., Schwartz, J. D., Pocock, B. J. Z., Monea, S., Whiting, D., Marcus, S. G., & Mignatti, P. (2001) · Journal of Cellular Physiology · doi:10.1002/jcp.10014 · Cited by 357
Matrix Metalloproteinase Gelatinase B (MMP-9) Coordinates and Effects Epithelial Regeneration
Mohan, R., Chintala, S. K., Jung, J. C., Villar, W. V. L., McCabe, F. J., Russo, L. A., Lee, Y., McCarthy, B. E., Wollenberg, K. R., Jester, J. V., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m107611200 · Cited by 307
Increased inflammation delays wound healing in mice deficient in collagenase‐2 (MMP‐8)
Gutiérrez‐Fernández, A., Inada, M., Balbı́n, M., Fueyo, A., Pitiot, A. S., Astudillo, A., Hirose, K., Hirata, M., Shapiro, S. D., Noël, A., et al. (2007) · The FASEB Journal · doi:10.1096/fj.06-7860com · Cited by 289
Tissue Inhibitor of Metalloproteinases-1 Is Decreased and Activated Gelatinases Are Increased in Chronic Wounds
Bullen, E. C., Longaker, M. T., Updike, D. L., Benton, R. L., Ladin, D. A., Hou, Z., & Howard, E. W. (1995) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12612786 · Cited by 271
Increased matrix metalloproteinase-9 (MMP-9) activity observed in chronic wound fluid is related to the clinical severity of the ulcer
Rayment, E. A., Upton, Z., & Shooter, G. K. (2008) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2008.08462.x · Cited by 253
Fibronectin Degradation in Chronic Wounds Depends on the Relative Levels of Elastase, α1-Proteinase Inhibitor, and α2-Macroglobulin
Grinnell, F., & Zhu, M. (1996) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12342990 · Cited by 232
The Transcriptional Activation Program of Human Neutrophils in Skin Lesions Supports Their Important Role in Wound Healing
Theilgaard‐Mönch, K., Knudsen, S., Follin, P., & Borregaard, N. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.12.7684 · Cited by 232
Activation of MMP‐9 by neutrophil elastase in an in vivo model of acute lung injury
Ferry, G., Lonchampt, M., Pennel, L., Nanteuil, G. D., Canet, E., & Tucker, G. C. (1997) · FEBS Letters · doi:10.1016/s0014-5793(96)01508-6 · Cited by 205
Matrix metalloproteinase-9 delays wound healing in a murine wound model
Reiss, M. J., Han, Y., Garcia, E., Goldberg, M. T., Yu, H., & Garner, W. L. (2009) · Surgery · doi:10.1016/j.surg.2009.10.016 · Cited by 193
Degradation of the epidermal-dermal junction by proteolytic enzymes from human skin and human polymorphonuclear leukocytes.
Briggaman, R. A., Schechter, N. M., Fraki, J., & Lazarus, G. S. (1984) · The Journal of experimental medicine · doi:10.1084/jem.160.4.1027 · Cited by 190
Preferential Inactivation of Tissue Inhibitor of Metalloproteinases-1 That Is Bound to the Precursor of Matrix Metalloproteinase 9 (Progelatinase B) by Human Neutrophil Elastase
Itoh, Y., & Nagase, H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.28.16518 · Cited by 189
Mice that lack matrix metalloproteinase-9 display delayed wound healing associated with delayed reepithelization and disordered collagen fibrillogenesis
Kyriakides, T. R., Wulsin, D., Skokos, E. A., Fleckman, P., Pirrone, A., Shipley, J. M., Senior, R. M., & Bornstein, P. (2009) · Matrix Biology · doi:10.1016/j.matbio.2009.01.001 · Cited by 173
Activation of matrix metalloproteinase 3 (stromelysin) and matrix metalloproteinase 2 (‘gelatinase’) by human neutrophil elastase and cathepsin G
Okada, Y., & Nakanishi, I. (1989) · FEBS Letters · doi:10.1016/0014-5793(89)80657-x · Cited by 167
Dynamics of the matrix metalloproteinases MMP‐1 and MMP‐8 in acute open human dermal wounds
Nwomeh, B. C., Liang, H., Diegelmann, R. F., Cohen, I. K., & Yager, D. R. (1998) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.1998.60206.x · Cited by 150
Up-regulation of elastase in acute wounds of healthy aged humans and chronic venous leg ulcers are associated with matrix degradation.
Herrick, S. E., Ashcroft, G. S., Ireland, G. W., Horan, M. A., McCollum, C. N., & Ferguson, M. W. J. (1997) · PubMed · Cited by 146
Inhibition of neutrophil elastase prevents cathelicidin activation and impairs clearance of bacteria from wounds
Cole, A. M., Shi, J., Ceccarelli, A., Kim, Y.-H., Park, A., & Ganz, T. (2001) · Blood · doi:10.1182/blood.v97.1.297 · Cited by 146
Proteolytic activity in wound fluids and tissues derived from chronic venous leg ulcers
Moor, A. N., Vachon, D. J., & Gould, L. J. (2009) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2009.00547.x · Cited by 126
Identification of the primary antimicrobial domains in human neutrophil cathepsin G.
Bangalore, N., Travis, J. W., Onunka, V. C., Pohl, J., & Shafer, W. M. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)77388-2 · Cited by 115
Wound Fluids: A Window Into the Wound Environment?
Yager, D. R., Kulina, R. A., & Gilman, L. A. (2007) · The International Journal of Lower Extremity Wounds · doi:10.1177/1534734607307035 · Cited by 108
α1-Antitrypsin Is Degraded and Non-Functional in Chronic Wounds But Intact and Functional in Acute Wounds: The Inhibitor Protects Fibronectin from Degradation by Chronic Wound Fluid Enzymes
Rao, C. N., Ladin, D. A., Chilukuri, K., Woodley, D. T., Liu, Y. Y., & Hou, Z. Z. (1995) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12323503 · Cited by 108
Catalytic activities of membrane‐type 6 matrix metalloproteinase (MMP25)
English, W., Velasco, G., Stracke, J. O., Knäuper, V., & Murphy, G. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02150-0 · Cited by 101
Collagenase‐2 (MMP‐8) and matrilysin‐2 (MMP‐26) expression in human wounds of different etiologies
Pirilä, E., Korpi, J. T., Korkiamäki, T., Jahkola, T., Gutierrez‐Fernandez, A., Lopez‐Otin, C., Saarialho‐Kere, U., Salo, T., & Sorsa, T. (2007) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2006.00184.x · Cited by 92
Sensor materials for the detection of human neutrophil elastase and cathepsin G activity in wound fluid
Hasmann, A., Geweßler, U., Hulla, E., Schneider, K. P., Binder, B., Francesko, A., Tzanov, T., Schintler, M., van der Palen, J. A. M., Guebitz, G. M., et al. (2011) · Experimental Dermatology · doi:10.1111/j.1600-0625.2011.01256.x · Cited by 70
Alternative Proteolytic Processing of Hepatocyte Growth Factor during Wound Repair
Buchstein, N., Hoffmann, D., Smola, H., Lang, S., Paulsson, M., Niemann, C., Krieg, T., & Eming, S. A. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.080597 · Cited by 68
Matrix metalloproteinase-8 overexpression prevents proper tissue repair
Danielsen, P. L., Holst, A. V., Maltesen, H. R., Bassi, M. R., Holst, P. J., Heinemeier, K. M., Olsen, J., Danielsen, C. C., Poulsen, S. S., Jørgensen, L. N., et al. (2011) · Surgery · doi:10.1016/j.surg.2011.06.016 · Cited by 55
Proteolytic Activation of Matrix Metalloproteinase-9 in Skin Wound Healing Is Inhibited by α-1-Antichymotrypsin
Han, Y., Yan, C., & Garner, W. L. (2008) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.77 · Cited by 53
Cellular resolution of inflammation—catabasis
Widgerow, A. D. (2012) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2011.00754.x · Cited by 48
Augmented Inflammatory Responses and Altered Wound Healing in Cathepsin G–Deficient Mice
Abbott, R. E. (1998) · Archives of Surgery · doi:10.1001/archsurg.133.9.1002 · Cited by 46
Pivotal Role for α1-Antichymotrypsin in Skin Repair
Hoffmann, D. C., Textoris, C., Oehme, F., Klaassen, T., Goppelt, A., Römer, A., Fugmann, B., Davidson, J. M., Werner, S., Krieg, T. M., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.249979 · Cited by 45
Skin wound healing in MMP2‐deficient and MMP2 / Plasminogen double‐deficient mice
Frøssing, S., Rønø, B., Hald, A., Rømer, J., & Lund, L. R. (2010) · Experimental Dermatology · doi:10.1111/j.1600-0625.2009.01062.x · Cited by 35
Paradoxical effects of elastase inhibitor guamerin on the tissue repair of two different wound models: sealed cutaneous and exposed tongue wounds
Lee, S. K., Lee, S. S., Song, I. S., Ys, K., Park, Y. W., Joo, J. Y., Um, H. S., Kim, J., Kim, K. Y., Choi, S. J., et al. (2004) · Experimental & Molecular Medicine · doi:10.1038/emm.2004.35 · Cited by 21
α1‐Antichymotrypsin activity correlates with and may modulate matrix metalloproteinase‐9 in human acute wounds
Reiss, M. J., Han, Y., & Garner, W. L. (2009) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2009.00476.x · Cited by 19

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Authors: Wilgus, T. A., Roy, S., & McDaniel, J. C.
Affiliations: The Ohio State University (US)
ORCID: Wilgus, Traci A.
Roy, Sashwati
McDaniel, Jodi C.
Venue: Advances in Wound Care
Publisher: SAGE Publications
Published: 2013-09
Volume: 2
Issue: 7
Pages: 379-388
ISSN: 2162-1918 (ISSN-L)
2162-1934
DOI: 10.1089/wound.2012.0383
PMC: PMC3763227
OpenAlex: W2045982747
Cited by: 616
References: 47
Citations by year: 2026: 58 · 2025: 66 · 2024: 84 · 2023: 64 · 2022: 63 · 2021: 66 · 2020: 66 · 2019: 38 · 2018: 34 · 2017: 35 · 2016: 23 · 2015: 13 · 2014: 4
FWCI: 2.23
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Advances in Wound Care (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Ohio State University (UL1RR025755)
National Institutes of Health (DK076566)
National Cancer Institute (R01CA127109)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK076566)
National Center for Research Resources (UL1RR025755)
Topics: Health Sciences › Medicine › Surgery › Wound Healing and Treatments
Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords: neutrophils, wound healing, skin wounds, chronic wounds, neutrophil proteases, tissue damage, delayed healing, scar formation, antimicrobial activity, wound infection

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Neutrophils and Wound Repair: Positive Actions and Negative Reactions

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