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Transendothelial migration of monocytes: the underlying molecular mechanisms and consequences of HIV-1 infection.

Maslin CL, Kedzierska K, Webster NL, Muller WA, Crowe SM

  • Journal Current HIV research

  • Published 27 Feb 2006

  • Volume 3

  • ISSUE 4

  • Pagination 303-17

  • DOI 10.2174/157016205774370401


Migration of monocytes from the bloodstream across vascular endothelium is required for routine immunological surveillance of tissues and their entry into inflamed sites. Transendothelial migration of monocytes initially involves tethering of cells to the endothelium, followed by loose rolling along the vascular surface, firm adhesion to the endothelium and diapedesis between the tightly apposing endothelial cells. A number of adhesion molecules are involved in this process. Monocyte rolling can be mediated by selectins and their ligands, or alpha(4)beta(1) integrin interacting with endothelial VCAM-1. On the apical surface of the endothelial cell, bound chemokines (eg. MCP-1, MIP-1alpha/beta) can activate leukocyte beta(2) integrins for tight adhesion to ICAM-1 and -2. Diapedesis by monocytes occurs through interaction between PECAM-1 on both the monocyte and the endothelial cells, followed by similar homophilic adhesion via CD99. After penetration of the endothelial basement membrane, monocytes migrate through the extracellular matrix of the tissues where they may differentiate into tissue macrophages and/or migrate to sites of inflammation. Additionally, monocytes in the tissues may traffic to the lymphatics or back into the bloodstream, both of which involve basal to apical (reverse) transendothelial migration, possibly mediated by tissue factor and p-glycoprotein. Monocyte trafficking is of current interest in studies of the pathogenesis of HIV-infection, including establishment of viral reservoirs in tissues and sanctuary sites and the development of HIV-related dementia. This review provides insights into the most recent studies on the process of monocyte migration across the vascular endothelium, and changes in migration that can occur during HIV-infection.