Differences in Cellular Infiltrate and Extracellular Matrix of Chronic Diabetic and Venous Ulcers Versus Acute Wounds
Open accessAbstract
In diabetic patients, wound healing is impaired. We studied the pathogenesis behind this clinical observation by characterizing the pattern of deposition of extracellular matrix (ECM) molecules and the cellular infiltrate in chronic (>8 wk) diabetic wounds, compared with chronic venous ulcers and an acute wound healing model. Punch biopsies were obtained from the chronic ulcer margins and control samples were collected from upper leg skin 5, 19, 28 d and 12 and 18 mo postwounding (p.w.). T cells, B cells, plasma cells, granulocytes and macrophages, and the ECM molecules fibronectin (FN), chondroitin sulfate (CS), and tenascin (TN) were visualized using immunohistochemical techniques. Expression of FN, CS, and TN was detected in dermal tissue early in normal wound healing (5-19 d p.w.). Abundant staining was seen 3 mo p.w., returning to prewounding levels after 12-18 mo p.w. In the dermis of chronic diabetic and venous ulcers with a duration of 12 mo or more, a prolonged presence of these ECM molecules was noted. Compared with normal wound healing: (i) the CD4/CD8 ratio in chronic wounds was significantly lower (p < 0.0027) due to a relatively lower number of CD4+ T cells; (ii) a significantly higher number of macrophages was present in the edge of both type of chronic ulcers (p < 0.001 versus day 29 p.w.); and (iii) more B cells and plasma cells were detected in both type of chronic wounds compared with any day in the acute wound healing model (p < 0.04 for CD20+ and p < 0.01 for CD79a+ cells). These data indicate that important differences exist in the cellular infiltrate and ECM expression patterns of acute, healing versus chronic wounds, which may be related to the nonhealing status of chronic wounds.
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Increased proinflammatory cellular infiltrates composed largely of neutrophils and macrophages contribute to delayed healing in chronic ulcers.
“It has been shown that increased proinflammatory cellular infiltrates composed largely of neutrophils and macrophages contribute to delayed healing in chronic ulcers (27, 28).”
From Wound repair and regeneration: Mechanisms, signaling, and translation (2014) · cites this paper as [28]
Chronic wounds are typically associated with a persistent inflammatory response that involves accumulation of macrophages.
“Chronic wounds are typically associated with a persistent inflammatory response that involves accumulation of Mp (19,26–28)”
From Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice (2014) · cites this paper as [26]
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- Authors
- Loots, M. A. M., Lamme, E. N., Zeegelaar, J., Mekkes, J. R., Bos, J. D., & Middelkoop, E.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Rode Kruis Ziekenhuis (NL)
- Corresponding author
- Loots, Miriam A.M.
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 1998-11
- Volume
- 111
- Issue
- 5
- Pages
- 850-857
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2079238808
- Cited by
- 620
- References
- 51
- Citations by year
- 2026: 23 · 2025: 18 · 2024: 25 · 2023: 20 · 2022: 28 · 2021: 35 · 2020: 39 · 2019: 32 · 2018: 28 · 2017: 31 · 2016: 34 · 2015: 28 · 2014: 27 · 2013: 30 · 2012: 27
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetic Foot Ulcer Assessment and Management
- Health Sciences › Medicine › Dermatology › Skin Diseases and Diabetes
- Keywords
- diabetic wounds, venous leg ulcers, chronic wounds, acute wound healing, extracellular matrix, fibronectin, chondroitin sulfate, tenascin, cellular infiltrate, CD4/CD8 ratio, macrophages, B cells, plasma cells, CD20, CD79a, delayed wound healing
- MeSH terms
- Acute Disease, Adult, Aged, Basement Membrane, Cell Count, Chondroitin Sulfates, Chronic Disease, Diabetes Mellitus, Type 1, Extracellular Matrix, Female, Fibronectins, Granulocytes, Humans, Lymphocytes, Macrophages, Male, Middle Aged, Varicose Ulcer, Wound Healing, Wounds and Injuries, CD4-CD8 Ratio, Diabetic Foot, CD8-Positive T-Lymphocytes, Tenascin
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