Endothelial-leukocyte adhesion molecule 1 stimulates the adhesive activity of leukocyte integrin CR3 (CD11b/CD18, Mac-1, alpha m beta 2) on human neutrophils.

Abstract

SummaryTwo classes of adhesion molecules have well-defined roles in the attachment of unstimulated polymorphonuclear leukocytes (PMN) to cytokine-treated endothelial cells. Endothelial-leukocyte adhesion molecule 1(ELAM-1) on endothelial cells interacts with specific carbohydrate residues on the PMN, and the leukocyte integrins (CD18 antigens) on PMN interact with intracellular adhesion molecule 1 and other structures on endothelium . Here we show that these two classes of molecules can act sequentially in an "adhesion cascade". Interaction of PMN with SLAM-1-bearing endothelial cells causes PMN to express enhanced adhesive activity of the integrin CR3 (CD11b/CD18) . Expression of ELAM-1 on the cytokine-treated endothelium appears both necessary and sufficient for the stimulation of CR3 activity since blockade of ELAM-1 with mAbs prevents the activation of CR3 by cytokine-treated endothelium, and immobilized recombinant ELAM-1 activates CR3 . The ability to activate CR3 is shared by chemattractants, suggesting that ELAM-1 may serve as a "tethered chemattractants" This hypothesis is strengthened by the observation that recombinant soluble ELAM-1 directs movement of PMN in chemotaxis chambers. These results suggest a mechanism by which multiple adhesive molecules may function together in diapedesis. ELAM-1 serves both as an adhesin and as a trigger that recruits the participation of additional adhesion molecules. Our results also suggest that ligands for adhesion molecules may also be "receptors" capable of generating intracellular signals.

Elevation of serum soluble E‐selectin and VCAM‐1 in severe asthma

“…14 sE-selectin is reported to be only a weak inhibitor of E-selectin-mediated adhesion, 15 while it may have cytokine-like functions that activate the polymorphonuclear cell CD11b integrin receptor, serving as a chemoattractant. 16 Furthermore, Th-1 lymphocytes, but not Th-2, are able to bind to E-selectin. 17 The particular increase of this selectin in severe asthma could suggest an involvement of Th-1 cells in addition to Th-2 in this group of patients.…”

Serum levels of soluble adhesion molecules in stem cell transplantation-related complications

“…sE-selectin directs movement of polymorphonuclear leukocytes and sICAM-1 mediates both activation of T cells and inhibition of cell adhesion to endothelial cells. [33][34][35] Thus, roles of these soluble adhesion molecules are complicated. Further study is needed to reveal their exact role in the development of chronic GVHD.…”

Evidence of an increased nitric oxide production in primary biliary cirrhosis

“…sICAM-1 has been shown to induce elastase release by PMNs and to participate as a priming stimulus in the production of reactive oxygen species in response to a second activating effector substance (32). On the other hand, E-selectin is particularly important in the early adhesion and rolling of neutrophils (33,34). From these observations, it could be hypothesized that extremely high sICAM-1 and sE-selectin amounts measured though nonspecific tests of neutrophil responses may reflect an enhanced PMN activation in PBC, as demonstrated by our findings of elevated neutrophil elastase concentrations mainly in this group of patients.…”