Monocyte trafficking across the vessel wall

Abstract

Monocytes fundamentally contribute to immune surveillance and the inflammatory response in immunoinflammatory diseases like atherosclerosis. Recruitment of these cells to the site of injury requires their trafficking across the blood vessel wall. A series of events, including capture, rolling, slow rolling, arrest, adhesion strengthening, and lateral locomotion, precede monocyte transmigration. Recent investigations have revealed new aspects of this cascade. This article revisits some conventional paradigms and selectively highlights new findings, including novel insights into monocyte differentiation and recently identified functional mediators, signalling pathways, and new structural aspects of monocyte extravasation. The emerging roles of endothelial junctional molecules like vascular endothelial-cadherin and the junctional adhesion molecule family, adhesion molecules such as intercellular adhesion molecule-1, molecules localized to the lateral border recycling compartment like cluster of differentiation 99, platelet/endothelial cell adhesion molecule-1, and poliovirus receptor (CD155), as well as other cell surface molecules such as cluster of differentiation 146 and ephrins in transendothelial migration are discussed.

Keywords: Extravasation; Monocyte migration; Monocyte subsets.

Figure 1

Schematic view of the monocyte adhesion cascade. ICAM-1, intercellular adhesion molecule-1; VCAM-1, vascular cell adhesion molecule-1; PECAM-1, platelet endothelial cell adhesion molecule; PSGL-1, P-selectin glycoprotein ligand-1; CD18 integrins, cluster of differentiation 18, beta subunit of integrins LFA-1 and Mac-1. A multistep cascade of capture, rolling, slow rolling, firm adhesion, adhesion strenghtening, and intraluminal crawling precedes the transendothelial migration of monocytes. Two modes of transmigration, a paracellular and a transcellular, can be distinguished. Activated endothelial cells express adhesion molecules and chemokines that interact with monocytic ligands. Such interactions essentially mediate the various steps of the adhesion cascade. This article focuses on how monocytes negotiate the endothelial monolayer.

Figure 2

Schematic view of paracellular monocyte transmigration. ICAM-1, intercellular adhesion molecule-1; PECAM-1, platelet endothelial cell adhesion molecule; CD99, cluster of differentiation 99; CD155, cluster of differentiation 155; VE-cadherin, vascular endothelial-cadherin; CD18 integrins, cluster of differentiation 18, beta subunit of integrins LFA-1 and Mac-1; JAMs, junctional adhesion molecules; LBRC, lateral border recycling compartment; NG2⁻, neuron-glial-2 negative. Vascular endothelial cell, red; monocyte, light blue; pericytes, red-brown. Monocyte extravasation into the site of inflammation requires transendothelial migration and penetration of the lamina basalis NG2⁻ pericytes. Monocytes transmigrate at sites of low matrix protein density. Monocyte engagement of endothelial cell surface molecules activates targeted recycling of the LBCR and thus enlarges the transmigration gap. The LBRC (brown) contains PECAM-1, CD99, CD155, and JAM-A, but not VE-cadherin, and supplies the transmigrating monocyte with additional functional molecules. VE-cadherin stabilizes junctional integrity in steady-state and transiently abandons site of transmigration under inflammatory conditions.