Chemokines IL-8, GRO alpha, 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 sk in repair model in adult humans, we investigated the role chemokines play i n sequential infiltration of leukocyte subsets during wound healing. At day 1 after injury, the C-X-C chemokines IL-8 and growth-related oncogene alph a are maximally expressed in the superficial wound bed and are spatially an d temporally associated with neutrophil infiltration. IL-8 and growth-relat ed oncogene alpha profiles also correlate with keratinocyte migration and s ubsequently subside after wound closure at dap 4. Macrophage infiltration r eaches the highest levels at day 2 and is paralleled by monocyte chemoattra ctant protein-1 mRNA expression in both the basal layer of the proliferativ e epidermis at the wound margins and mononuclear cells in the wound area. O ther monocyte-attracting chemokines such as monocyte chemoattractant protei n-3, macrophage inflammatory protein-1 alpha and -1 beta, RANTES, and 1309 are undetectable. At day 4, perivascular focal lymphocyte accumulation corr elates 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 spa tially and temporally different infiltration of leukocyte subsets and thus integrates the inflammatory and reparative processes during wound repair.