MIP-1alpha as a critical macrophage chemoattractant in murine wound repair.

Abstract

At sites of injury, macrophages secrete growth factors and proteins that promote tissue repair. While this central role of the macrophage has been well studied, the specific stimuli that recruit macrophages into sites of injury are not well understood. This study examines the role of macrophage inflammatory protein 1 ␣ (MIP-1 ␣ ), a C-C chemokine with monocyte chemoattractant capability, in excisional wound repair. Both MIP-1 ␣ mRNA and protein were detectable in murine wounds from 12 h through 5 d after injury. MIP-1 ␣ protein levels peaked 3 d after injury, coinciding with maximum macrophage infiltration. The contribution of MIP-1 ␣ to monocyte recruitment into wounds was assessed by treating mice with neutralizing anti-MIP-1 ␣ antiserum before injury. Wounds of mice treated with anti-MIP-1 ␣ antiserum had significantly fewer macrophages than control (41% decrease, P Ͻ 0.01). This decrease in wound macrophages was paralleled by decreased angiogenic activity and collagen synthesis. When tested in the corneal micropocket assay, wound homogenates from mice treated with anti-MIP-1 ␣ contained significantly less angiogenic activity than control wound homogenates (27% positive for angiogenic activity versus 91% positive in the control group, P Ͻ 0.01). Collagen production was also significantly reduced in the wounds from anti-MIP-1 ␣ treated animals (29% decrease, P Ͻ 0.05). The results demonstrate that MIP-1 ␣ plays a critical role in macrophage recruitment into wounds, and suggest that appropriate tissue repair is dependent upon this recruitment. (

Expression of CCR2 by Endothelial Cells

“…This suggests that MCP-1 predominantly acts by inducing migration during endothelial wound injury. Our results expand findings that MCP-1 and MIP-1␣ are critical in wound repair by mediating macrophage recruitment 43,44 and that MCP-1 may facilitate angiogenesis, 23 implying that these processes are in part due to endothelial mechanisms.…”

Chemokines in Wound Healing and as Potential Therapeutic Targets for Reducing Cutaneous Scarring

“…Murine skin wound healing models have demonstrated that CCL2, CCL3, and CCL5 also play critical roles in macrophage recruitment. [50][51][52][53][54] Macrophages are essential for normal wound repair providing a source of cytokines, growth factors, and chemokines. 44,50,55 Once recruited, the wound microenvironment strongly influences phenotypic polarization of macrophages enabling functional heterogeneity through differential chemokine, cytokine, and receptor repertoires (Fig.…”

Differential Expression of CC Chemokines and the CCR5 Receptor in the Pancreas Is Associated with Progression to Type I Diabetes

“…Immediately before analysis, tissues were homogenized and sonicated in an antiprotease buffer (Roche, Laval, Canada) as previously described (21)(22)(23)(24). Homogenates were centrifuged to remove debris and were then passed through 1.2-m pore size filters (Gelman Sciences, Ann Arbor, MI).…”