Efferocytosis as a regulator of macrophage chemokine receptor expression and polarization. Issue 7 (20th May 2016) - Angsana, Julianty
Abstract : Two mechanisms have been proposed to explain macrophage clearance: local cell death and emigration to draining lymphatics. The latter mechanism suggests motility‐dependent resolution and provides significant motivation to characterize directed migration in polarized macrophages. Through qPCR, flow cytometry, in vitro and in vivo motility assays, we identified enhanced expression of CXCR4 on resolving macrophages and confirmed a role for CXCR4 in the resolution of murine peritonitis. Abstract : Efferocytosis has been suggested to promote macrophage resolution programs that are dependent on motility and emigration, however, few studies have addressed directed migration in resolving macrophages. In this report, we hypothesized that efferocytosis would induce differential chemokine receptor expression. Polarized macrophage populations, including macrophages actively engaged in efferocytosis, were characterized by PCR array and traditional transwell motility assays. We identified specific up‐regulation of chemokine receptor CXCR4 on both mouse and human macrophages and characterized in vivo expression of CXCR4 in a resolving model of murine peritonitis. Using adoptive transfer and AMD3100 blocking, we confirmed a role for CXCR4 in macrophage egress to draining lymphatics. Collectively these data provide an important mechanistic link between efferocytosis and macrophage emigration.