‘This way please’: Apoptotic cells regulate phagocyte migration before and after engulfment

Apoptotic leukocyte clearance is a hallmark of the resolution of inflammation and is a central fate-determining event for macrophages. The directional migration of motile phagocytes toward cellular corpses and the subsequent engulfment are tightly regulated, and the exciting molecular mechanisms for these complex steps are actively under investigation. In this issue Angsana et al. [Eur. J. Immunol. 2016. 46: XXXX-XXXX. DOI 10.1002/eji.201546262] report that the chemokine receptor CXCR4 is upregulated on murine and human macrophages following the engulfment of apoptotic cells, or following exposure to the pro-resolving nucleotide adenosine. This work, together with other recent findings, point toward a new mode of regulation of macrophages following the engulfment of apoptotic cells. In this commentary, we put these findings in relevant perspective and highlight its potential ramifications.

Directional migration of monocytes/macrophages is controlled by apoptotic cells. (i) During the resolution of inflammation apoptotic leukocytes release "find-me" signals that bind specific GPCRs on the surface of monocytes/macrophages and attract them toward leukocyte corpses to enhance efferocytosis. (ii) Following efferocytosis, macrophages upregulate CXCR4 and depart to remote CXCL12-producing organs.

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