Monocytes on the beaten track
In inflammatory responses recruitment of monocytes is classically preceeded by a wave of emigrating neutrophils. The existence of a causal link between these two events has repeatedly been shown but the underlying mechanisms remain controversial. Recently Wantha and colleagues have reported an important role of neutrophil-derived cathelicidin for the adhesion of classical monocytes.
Mechanistically the authors show that neutrophil-derived cathelicidins (human: LL37, mouse: CRAMP) induce adhesion of classical monocytes but not of non-classical monocytes in the mouse cremaster muscle and in in vitro flow chamber assays. CRAMP is released from emigrated neutrophils and then transported across the endothelium where it is presented to rolling leukocytes. The transport across the endothelium is an active, caveolin-dependent mechanism. Endothelial-bound cathelicidin activates FPR2 on classical monocytes, resulting in monocytic β1- and β2-integrin conformational change towards an extended, active conformation that allows for adhesion to their respective ligands VCAM-1 and ICAM-1. Conclusively, these data elucidate a novel mechanism of neutrophil-mediated monocyte recruitment, which could be targeted in conditions where recruitment of classical monocytes plays an unfavorable role. Atherosclerosis could be one of these conditions – and indeed the authors have previously shown that lack of cathelicidin reduces monocyte recruitment and atherosclerotic lesion burden.
The significance of the work by Wantha et al. is underlined by an editorial commentary from Fil Swirski and Clinton Robbins (http://circres.ahajournals.org/content/112/5/744.full) as well as an editorial highlight (http://circres.ahajournals.org/content/112/5/743.full).
Publication:
Neutrophil-Derived Cathelicidin Promotes Adhesion of Classical Monocytes.
Sarawuth Wantha, Jean-Eric Alard, Remco T.A. Megens, Anne M. van der Does, Yvonne Döring, Maik Drechsler, Christine T.N. Pham, Ming-Wei Wang, Ji-Min Wang, Richard L. Gallo, Philipp von Hundelshausen, Lennart Lindbom, Tilman Hackeng, Christian Weber, and Oliver Soehnlein. Circulation Research. 2013;112:792-801, published online before print January 2 2013, doi:10.1161/CIRCRESAHA.112.300666.
