In this study, we show that macrophage activation by TLR ligands LPS and polyinosinic-polycytidylic acid induced a time-dependent increase of Sema4A and its receptors PlexinB2 and PlexinD1. Moreover, in a thioglycollate-induced peritonitis mouse model, Sema4A was detected in circulating Ly6C(high) inflammatory monocytes and peritoneal macrophages.
Acting via PlexinD1, exogenous Sema4A strongly increased macrophage migration.
Of note, Sema4A-activated PlexinD1 enhanced the expression of vascular endothelial growth factor-A, but not of inflammatory chemokines. Sema4A-stimulated macrophages were able to activate vascular endothelial growth factor receptor-2 and the PI3K/serine/threonine kinase Akt pathway in endothelial cells and to sustain their migration and in vivo angiogenesis. Remarkably, in an in vivo cardiac ischemia/reperfusion mouse model, Sema4A was highly expressed in macrophages recruited at the injured area.
We conclude that Sema4A activates a specialized and restricted genetic program in macrophages able to sustain angiogenesis and participates in their recruitment and activation in inflammatory injuries.
JournalJournal of immunology
J Immunol (1550-6606)
Department of Oncological Sciences, University of Torino School of Medicine, 10060 Candiolo, Italy.
J Immunol. 2012 Apr;188(8):4081-92
Español | English
© Galenicom 1999-2013