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.
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.
Engelhardt
E
E
Department of Dermatology, University of Würzburg Medical School, Germany.
Toksoy
A
A
Goebeler
M
M
Debus
S
S
Bröcker
E B
EB
Gillitzer
R
R
D000328:Adult; D002455:Cell Division; D018932:Chemokine CCL2 / Q000378:metabolism; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism; D002630:Chemotactic Factors / Q000378:metabolism; D005260:Female; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000502:physiology; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014945:Wound Healing / Q000276:immunology*
C475829:CXCL1 protein, human; C080810:CXCL9 protein, human; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D012333:RNA, Messenger