ICAM-1 Signaling and Role in Leukocyte Migration

ICAM-1 (and not so abundantly expressed VCAM-1) are essential components in leukocyte migration across or even through edothelial cells. Endothelial cells make up the barrier between blood vessels and neighboring system, like the brain. The blood brain barrier is actually composed of a highly selective layer of endothelial cells that are interwoven with both tight junctions and adherins. Transendothelial migration or TEM, can be induced by pro-inflammatory factors such as TNF[alpha]. It can activate a number of signaling pathways, including one culmination in NF-kB activation. TNF[alpha] can upregulate the expression of strong adhesion ICAM-1 on the surface of endothelial cells. They cluster on the outer cell membrane and attach to expressed adhesion molecule, LFA-1, on circulating leukocytes. This recruits leukocytes to endothelial cells and induces rolling. TEM can occur either transcellularly or paracellularly. In the case of crossing the BBB, a transcellular pathway is preferential, as it does not require the disruption of tight junctions. It is unclear whether ICAM-1 is drawn into internal compartments or special organelles called LBRCs with the aid of caveolin-1 and formation of caveolae and onto MVBs. The later seems more plausible, but may also involve the internalization of of VE-cadherins. Leukocyte binding or other ligation to ICAM-1 may trigger a number of responses including activation of c-Fos and c-Jun transcription factors to upregulate ICAM-1. It may also cause the build up of ROS through NADPH oxidase activation, and thereby activating NF-[kappa]B and increase production of ICAM-1 and cytokines. ROS also contributes to cytoskeletal changes, which is necessary for the clustering of ICAM-1.

I also went to a presentation for WMSURE and PLUS students given by assistant professor Dr. Shante Hinton. Her research centers around tyrosine phosphorylation or particular proteins, like MK-STX. This protein is believed to be highly important is management of stress granules, cell proliferation and growth. The mismanagement of MK-STX and components of its signalling pathways has been related to degenerative diseases. She is a leading researcher in the field of tyrosine phosphorylation and I look forward to speaking and even possibly working with her in the future.