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Macrophages are essential for the early wound healing response and the formation
of a fibrovascular scar
#MMPMID23602833
He L
; Marneros AG
Am J Pathol
2013[Jun]; 182
(6
): 2407-17
PMID23602833
show ga
After wounding, multiple cell types interact to form a fibrovascular scar; the
formation and cellular origins of these scars are incompletely understood. We
used a laser-injury wound model of choroidal neovascularization in the eye to
determine the spatiotemporal cellular events that lead to formation of a
fibrovascular scar. After laser injury, F4/80(+) myeloid cells infiltrate the
wound site and induce smooth muscle actin (SMA) expression in adjacent retinal
pigment epithelial cells, with subsequent formation of a SMA(+)NG2(+)
myofibroblastic scaffold, into which endothelial cells then infiltrate to form a
fibrovascular lesion. Cells of the fibrovascular scaffold express the
proangiogenic factor IL-1? strongly, whereas retinal pigment epithelial cells are
the main source of VEGF-A. Subsequent choroidal neovascularization is limited to
the area demarcated by this myofibroblastic scaffold and occurs independently of
epithelial- or myeloid-derived VEGF-A. The SMA(+)NG2(+) myofibroblastic cells,
F4/80(+) macrophages, and adjacent epithelial cells actively proliferate in the
early phase of the wound healing response. Cell-lineage tracing experiments
suggest that the SMA(+)NG2(+) myofibroblastic scaffold originates from choroidal
pericyte-like cells. Targeted ablation of macrophages inhibits the formation of
this fibrovascular scaffold, and expression analysis reveals that these
macrophages are Arg1(+)YM1(+)F4/80(+) alternatively activated M2-like
macrophages, which do not require IL-4/STAT6 or IL-10 signaling for their
activation. Thus, macrophages are essential for the early wound healing response
and the formation of a fibrovascular scar.
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