Endothelial basement membrane laminins as an environmental cue in monocyte differentiation to macrophages.

BioRxiv : the Preprint Server for Biology
L. LiLydia Sorokin

Abstract

Monocyte extravasation is a trigger for differentiation to macrophages. Intravital imaging of CCL2-induced extravasation of CX3CR1-GFP immune cells in mice lacking integral endothelial basement membrane (BM) laminins, Lama4-/- and Tek-cre::Lama5-/-, revealed higher motility of CX3CR1-GFPlow inflammatory-monocytes at laminin 511low sites. In vitro experiments revealed that this is not due to direct effects of laminin 511 on migration modes, nor effects on the tightness of the endothelial barrier. Rather, using an intestinal macrophage replenishment model and in vitro differentiation studies we demonstrate that endothelial BM laminin 511 uniquely promotes monocyte differentiation to macrophages. This is associated with a change in integrin profile, permitting differentiating macrophages to distinguish between laminin 511 high and low areas and to migrate preferentially across laminin 511 low sites. These studies highlight the endothelial BM as a critical site for monocyte switch to macrophages, and may be relevant to the differentiation of other cells at vascular niches.

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