Chemokines IL-8, GROalpha, MCP-1, IP-10, and Mig are sequentially and differentially expressed during phase-specific infiltration of leukocyte subsets in human wound healing

Am J Pathol. 1998 Dec;153(6):1849-60. doi: 10.1016/s0002-9440(10)65699-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Division
  • Chemokine CCL2 / metabolism
  • Chemokine CXCL1
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines / metabolism*
  • Chemokines, CXC / metabolism
  • Chemotactic Factors / metabolism
  • Female
  • Growth Substances / metabolism
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Intercellular Signaling Peptides and Proteins*
  • Interleukin-8 / metabolism
  • Keratinocytes / physiology
  • Leukocytes / immunology*
  • Male
  • Middle Aged
  • Neovascularization, Physiologic
  • RNA, Messenger / metabolism
  • Time Factors
  • Wound Healing / immunology*

Substances

  • CXCL1 protein, human
  • CXCL9 protein, human
  • Chemokine CCL2
  • Chemokine CXCL1
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines
  • Chemokines, CXC
  • Chemotactic Factors
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-8
  • RNA, Messenger