Lung Inflammation and Adhesion Molecules

Abstract

Adhesion molecules have been shown to be important in inducing inflammatory responses in experimental animals. The topic has recently been the subject of a fairly extensive review (Harlan and Liu, 1992). Adhesion molecules on endothelial cells and leukocytes are diverse, and can be divided into two groups: those that are constitutively expressed, and those that are inducible after endothelial cell contact with appropriate stimuli. Table I presents some of the adhesion molecules of endothelial cells and neutrophils that are most important in the inflammatory response. In this context, the chief difference between endothelial cells and leukocytes is that adhesion molecules are generally not constitutively expressed on the former, whereas they are on the latter. ICAM-1 and -2 are normally constitutively expressed in small amounts on endothelial cells. When endothelial cells are stimulated with TNFα, IL-1, or endotoxin, gene activation occurs, and ICAM expression is slowly but steadily increased over the next 12 hr. Also triggered is the gene controlling expression of E-selctin (ELAM-1), with maximal expression developing in about 4 hr. P-selectin is an exception to the requirement for protein synthesis; this glycoprotein is stored in the Weibel-Palade granules of endothelial cells (and in the alpha granules of platelets), and can be rapidly translocated (in 5-10 min) to the endothelial cell surface after the addition of histamine or thrombin. The most recently described adhesionpromoting molecule of the endothelial cell is Gly-CAM-1, a heavily glycosylated protein which, unlike the other adhesion molecules, has no transmembranespanning segment and appears to be entirely extracellular, embedded in the glycocalyx of the endothelial cells (Lasky et al., 1992). VCAM-1 is another adhesion-promoting molecule of endothelial cells. This glycoprotein is not normally expressed; it appears on the cell surface approximately 4 hr after stimulation, with expression being retained for the next 12-18 hr. “Counterreceptors” for these adhesion molecules are diverse (Table I). In the case of ICAM-1 and -2, the complementary reactive molecules on leukocytes are the β2 integrins (LFA-1 and Mac-1, see below). E- and P-selectin react with leukocytic lectins, which are Oligosaccharides of the structure sialyl Lewis^x and sialyl Lewis^a (reviewed by Harlan and Liu, 1992). Gly-CAM-l appears to be the lectin-containing molecule that is reactive with leukocytic L-selectin (see below).