Origin and function of the repair macrophage in the murine sterile wound

Abstract

Experiments were performed to define the phenotype and origin of repair macrophages (mφ). Wound cells were isolated from 1 to 14 days following subcutaneous insertion of sterile polyvinyl alcohol sponges in mice and examined for monocyte/mφ markers by flow cytometry. F4/80+Ly6Chi cells with an inflammatory monocyte signature appeared early, followed by accumulation of F4/80+Ly6Clow/int repair‐like mφ. Ly6Chi wound monocytes expressed CD64 but not the mφ marker Mer tyrosine kinase (MerTK), similar to blood monocyte precursors. In contrast to blood monocytes, wound monocytes upregulated CD14 and had a proinflammatory cytokine production profile. F4/80+Ly6Clow/int mφ were CD64+MerTK+ and produced cytokines associated with repair including VEGF and TGF‐β. Examination of CX3CR1‐GFP mice and selective labeling of circulating monocyte subsets demonstrated that Ly6Chi monocytes preferentially migrated from the blood to the wound. Analysis of cells from adoptively transferred sponges suggested that Ly6Chi monocytes mature within the wound to become Ly6Clowmφ. Overall, these studies functionally and phenotypically distinguished wound monocyte/mφ subsets and identified MerTK as a potential marker for repair mφ during sterile inflammation. Research supported by R01 GM042859, K08 GM079227 and the RIH Department of Surgery.