Chemokines IL-8, GROα, MCP-1, IP-10, and Mig Are Sequentially and Differentially Expressed During Phase-Specific Infiltration of Leukocyte Subsets in Human Wound Healing

Engelhardt, Eva; Toksoy, Atiye; Goebeler, Matthias; Debus, Sebastian; Bröcker, Eva-Bettina; Gillitzer, Reinhard

doi:10.1016/s0002-9440(10)65699-4

Cited by 435Wound Healing and TreatmentsChemokine receptors and signalingInflammation biomarkers and pathways

Chemokines IL-8, GROα, MCP-1, IP-10, and Mig Are Sequentially and Differentially Expressed During Phase-Specific Infiltration of Leukocyte Subsets in Human Wound Healing

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Engelhardt, Eva, Toksoy, Atiye, Goebeler, Matthias, Debus, Sebastian, Bröcker, Eva-Bettina, Gillitzer, Reinhard·1998·The American Journal of Pathology

DOI 10.1016/s0002-9440(10)65699-4PMC PMC1866330

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Abstract

Healing of cutaneous wounds requires a complex integrated network of repair mechanisms, including the action of newly recruited leukocytes. Using a skin repair model in adult humans, we investigated the role chemokines play in sequential infiltration of leukocyte subsets during wound healing. At day 1 after injury, the C-X-C chemokines IL-8 and growth-related oncogene alpha are maximally expressed in the superficial wound bed and are spatially and temporally associated with neutrophil infiltration. IL-8 and growth-related oncogene alpha profiles also correlate with keratinocyte migration and subsequently subside after wound closure at day 4. Macrophage infiltration reaches the highest levels at day 2 and is paralleled by monocyte chemoattractant protein-1 mRNA expression in both the basal layer of the proliferative epidermis at the wound margins and mononuclear cells in the wound area. Other monocyte-attracting chemokines such as monocyte chemoattractant protein-3, macrophage inflammatory protein-1alpha and -1beta, RANTES, and 1309 are undetectable. At day 4, perivascular focal lymphocyte accumulation correlates with strong focal expression of the C-X-C chemokines Mig and IP-10. Our results suggest that a dynamic set of chemokines contributes to the spatially and temporally different infiltration of leukocyte subsets and thus integrates the inflammatory and reparative processes during wound repair.

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Lower MIG/CXCL9 levels suggest poor remodelling of the wound tissue.
“In the THS-exposed mouse wounds [65] the levels of this chemokine are lower after 5 days post-wounding suggesting poor remodelling of the wound tissue.”
From Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing (2016) · cites this paper as [65]
The Discussion (page unavailable) links Mig to lymphocyte accumulation and suggests that lymphocytes influence tissue repair and remodeling. That provides a rationale for the inference, but the paper studies normal human wounds; it does not show that lower Mig levels predict poor remodeling in THS-exposed mouse wounds. (LLM, conf=0.85)
Experimental — accuracy not yet measured
MIG/CXCL9 levels are lower after 5 days post-wounding in THS-exposed mouse wounds.
“In the THS-exposed mouse wounds [65] the levels of this chemokine are lower after 5 days post-wounding suggesting poor remodelling of the wound tissue.”
From Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing (2016) · cites this paper as [65]
The Results section on Mig, IP-10, and MCP-1 describes Mig expression after day 4 in normally healing human wounds, not THS-exposed mouse wounds. Our copy does not report Mig/CXCL9 levels in THS-exposed mice or a decrease after day 5; searches for those terms found no such result. (LLM, conf=0.78)
Experimental — accuracy not yet measured
Neutrophils are the most abundant inflammatory cells to infiltrate a new wound and function mainly to remove debris and prevent infection.
“Neutrophils represent the most abundant inflammatory cells to infiltrate a new wound and function mainly to remove debris and prevent infection [22, 23].”
From Immunology of Wound Healing (2018) · cites this paper as [22]

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Authors: Engelhardt, E., Toksoy, A., Goebeler, M., Debus, S., Bröcker, E.-B., & Gillitzer, R.
Affiliations: University of Würzburg (DE)
Corresponding author: Gillitzer, Reinhard
ORCID: Engelhardt, Eva
Goebeler, Matthias
Venue: The American Journal of Pathology
Publisher: Elsevier BV
Published: 1998-12
Volume: 153
Issue: 6
Pages: 1849-1860
ISSN: 0002-9440 (ISSN-L)
DOI: 10.1016/s0002-9440(10)65699-4
PMC: PMC1866330
OpenAlex: W2010087085
Cited by: 435
References: 64
Citations by year: 2026: 8 · 2025: 12 · 2024: 12 · 2023: 15 · 2022: 9 · 2021: 17 · 2020: 15 · 2019: 12 · 2018: 18 · 2017: 25 · 2016: 10 · 2015: 15 · 2014: 20 · 2013: 13 · 2012: 23
FWCI: 17.08
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: American Journal Of Pathology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords: chemokines, wound healing, skin wound healing, leukocyte infiltration, neutrophil infiltration, macrophage infiltration, keratinocyte migration, interleukin-8, CXCL1, MCP-1, CXCL10, CXC chemokines, skin inflammation, lymphocyte accumulation, spatiotemporal gene expression
MeSH terms: Adult, Cell Division, Chemotactic Factors, Female, Growth Substances, Humans, Immunohistochemistry, Leukocytes, Male, Middle Aged, RNA, Messenger, Time Factors, Wound Healing, Keratinocytes, Interleukin-8, In Situ Hybridization, Neovascularization, Physiologic, Chemokines, Chemokine CCL2, Chemokines, CXC, Intercellular Signaling Peptides and Proteins, Chemokine CXCL10, Chemokine CXCL1, Chemokine CXCL9

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Chemokines IL-8, GROα, MCP-1, IP-10, and Mig Are Sequentially and Differentially Expressed During Phase-Specific Infiltration of Leukocyte Subsets in Human Wound Healing

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