Postulated pathway by which MCP-1, MIP-1α and MIP-2 interact in the inflammatory tissue healing cascade.
MCP-1 activates fibroblasts, smooth muscle cells, and monocytes and macrophages. Recruited bone marrow derived monocytes and macrophages release a variety of cytokines including MIP-1α, MIP-2, matrix metalloproteinases, IL-1, and others, which induce further monocyte and macrophage infiltration via autocrine activation. MIP-1α is upregulated by the interaction between macrophages and fibroblasts, and in turn, induces secretion of TNFα which upregulates ICAM-1 expression by fibroblasts, endothelial cells, and macrophages. MIP-1α and MIP-2, which are secreted by activated macrophages, directly recruit the migration of neutrophils, macrophages, and other leukocytes to the site of injury and repair.