Leukocyte transmigration

Weber, C. (2003). Novel mechanistic concepts for the control of leukocyte transmigration Specialization of integrins, chemokines, and junctional molecules. I. Mol. Med. 81, 4-19. 

Figure 14.1 Leukocyte transmigration. Expression of P- and E-selectins (and integrins) on the endothelial surface of damaged cells weakly binds leukocyte carbohydrate ligands, slowing and causing the leukocyte to roll over the endothelial surface, eventually holding the leukocyte in place.

Rival Y, Del-Maschio A, Rabiet MJ, et al. Inhibition of platelet endothelial cell adhesion molecule-1 synthesis and leukocyte transmigration in endothelial cells by the combined action of TNF-a and IFN-y. J Immuno 1996 157 1233-41. 

Figure 4.1. Schematic representation of leukocyte transmigration induced by chemokines. The first step involves rolling attributed to interaction between the leukocyte and the endothelial cells. This process is mediated by selectins and selectin ligands expressed on the surface of both cell types. In the next step a chemokine interacts with its receptor, inducing leukocyte activation and conformational changes in the adhesion molecules (integrins) and resulting in firm adhesion to the endothelial surface. It is believed that the chemokine is immobilized on the endothelial surface by interactions with glycosaminoglycans. The leukocytes then transmigrate into the tissues.

Shaw SK, Perkins BN, LimYC, LiuY, Nusrat A, Schnell FJ, Parkos CA, Luscinskas FW Reduced e q)ression of junctional adhesion molecule and platelet/endothelial cell adhesion molecule-1 (CD31) at human vascular endothelial junctions by cytokines tumor necrosis factor-alpha plus interferon-gamma does not reduce leukocyte transmigration under flow. Am J Pathol 2001 ... 

Allport JR, Ding H, Collins T, Gerritsen ME, Luscinskas FW Endothelial-dependent mechanisms regulate leukocyte transmigration A process involving the proteasome and disruption of the vascular endothelial-cadherin complex at endothelial cell-to-cell junctions. J Exp Med 1997 186 517-527. 

Muller WA. Leukocyte-endothelial-ceU interactions in leukocyte transmigration and the inflammatory response. Trends Immunol 2003 24 327-334. 

The effect of TNF-a blockade on this rat model also has been tested (67). Anti-rat TNF monoclonal antibodies were administered after glomerulonephritis was established. This treatment significantly reduced albuminuria and prevented crescent formation (0% treated vs. 60% controls). Lung hemorrhage was also reduced. When analyzed by intravital microscopy, there was a 43% inhibition of leukocyte transmigration in mesenteric venules in response to topical cytokine stimulation. This amelioration of disease occurred with no difference in anti-MPO antibody titers. This ameliorating effect of anti-TNF was similar to the affect of anti-TNF treatment in the mouse model of ANCA-associated vasculitis caused by injection of anti-MPO antibodies (61). 

Migration across the endothelium, known as transmigration, occurs via the process of diapedesis. Chemokine gradients stimulate the adhered leukocytes to move between endothelial cells and pass the basement membrane into the tissues. 

ICAM-1, also known as CD54 (cluster of differentiation 54), is a human gene. The protein encoded by this gene is a type of intercellular adhesion molecule, normally present in low concentrations in the membranes of leukocytes and endothelial cells upon cytokine stimulation (particularly IL-1 and TNF-a) the concentrations greatly increase. ICAM-1 is a ligand for LFA-1 (integrin), a receptor found on leukocytes. When activated, leukocytes bind to endothelial cells via ICAM-1/LFA-1 and then transmigrate into tissues. 

Brundula V, Rewcastle NB, Metz LM, Bernard CC, Yong VW (2002) Targeting leukocyte MMPs and transmigration minocychne as a potential therapy for multiple sclerosis. Brain 125 1297-1308. 

Intestinal inflammation In an animal model of Crohn s disease (hapten-induced cohtis), ZK-192 administered after disease onset displayed anti-inflammatory bioactions reducing TNF-, interferon-y and interleukin-8 LX modulates neutrophil transmigration across the intestinal epithelial monolayer, inhibits leukocyte rolling and adherence, modulates interleukin-8 release chemokine secretion LX inhibits TNl -o-induced nculrophil-cnlcrocyle interaction, chemokine release and colonocyte apoptosis Fiorucci et al. 2004... 

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