Adhesion molecules
Chapter: 2
Adhesion molecules (see text pp. 49-52; Fig. 2-15) are molecules on the surfaces of cells that assist leukocytes in interacting with their environments through adherence. They are qualitatively and quantitatively changed on the surfaces of endothelial cells and leukocytes during inflammation. Leukocytes in the circulation are "swimming" in the axial zone (central stream) of flowing blood, rarely interacting with the walls of the vessels through which they pass. In inflammatory settings, they peripheralize, i.e., move out of the axial stream, toward the wall, where they begin to become activated and their surfaces have the opportunity to interact with the surfaces of endothelial cells. Such interactions are perpetuated by a variety of adhesion molecules, allowing the leukocytes to attach, tightly adhere, and then to begin crawling on the surfaces of endothelial cells and, subsequently, other substrata (such as collagen, once they have transmigrated into the extravascular tissues). Members of the lectin-like group referred to as selectins (GMP-140, a.k.a. P-selecting; ELAM-1; and LAM-1) tend to initiate leukocyte attachment. The integrins, which are a group of glycoproteins expressed on both leukocytes and endothelial cells, then intensify adherence. Adherence is promoted further by endothelial adherence molecules, such as ICAM-1. Adhesion molecules also assist phagocytic leukocytes in adhering to particles that they want to ingest. The kinds and numbers of adhesion molecules can be changed on the surfaces of cells by the pharmacologic effects of proinflammatory mediators, during the process of activating leukocytes for inflammatory functions. Some inducible genes, which are key to augmentation and amplification of the initial inflammatory response, cannot be expressed until leukocytes become adherent -- another part of the fail-safe check and balance system that serves to constrain the inlammatory process until it is needed.