A novel leukointegrin, αdβ2, binds preferentially to ICAM-3

Abstract

The leukocyte-restricted beta 2 (CD18) integrins mediate cell adhesion in a variety of events essential for normal immune function. Despite extensive research in this field, only three members of this integrin subfamily have been described: CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1), and CD11c/CD18 (p150,95). We have identified a cDNA encoding a fourth alpha chain, alpha d, that associates with CD18. The alpha d subunit is more closely related to CD11b and CD11c than to CD11a. This integrin is expressed at moderate levels on myelomonocytic cell lines and subsets of peripheral blood leukocytes, and more strongly on tissue-compartmentalized cells such as foam cells, specialized macrophages found in aortic fatty streaks that may develop into atherosclerotic lesions. The alpha d/CD18 molecule exhibits preferential recognition of ICAM-3 over ICAM-1.

Synovial distribution of αd/CD18, a novel leukointegrin. Comparison with other integrins and their ligands

“…Alternatively, it may represent a feature of the memory phenotype of T cells recruited into the synovium. Expression of this molecule on the myeloid lines HL60 and THP-1 is reduced by stimulation with PMA, whereas expression of CDllb and CDllc is increased (6). Studies of a d levels in both PBL and synovium from RA patients, as well as comparisons with other inflammatory states, will be needed to further clarify this issue.…”

“…ad/ CDl8 is expressed at very low levels. Granulocytes and monocytes express high levels of CDllb, with lower levels of CDlla, CDllc, and ad (4,6,19). Stimulation of granulocytes with phorbol myristate acetate (PMA) or FMLP results in a rapid increase in the levels of a d expression, consistent with mobilization of an intracellular pool of a d in these cells (6).…”

Integrin αDβ2, an adhesion receptor up-regulated on macrophage foam cells, exhibits multiligand-binding properties

“…However, the pattern of expression of this integrin is unique among other myeloid cellspecific ␤ 2 integrins in that ␣ D ␤ 2 is expressed poorly on peripheral blood leukocytes but strongly on macrophage foam cells within atherosclerotic plaques. 1,2 In contrast, the major myeloid-specific integrin ␣ M ␤ 2 is progressively up-regulated on circulating neutrophils and monocytes in response to chemotactic stimulation 3,4 and is down-regulated in lesion-derived macrophages. 5 The significance of the up-regulation of ␣ D ␤ 2 in monocyte-derived cells from atherosclerotic lesions is not known.…”

“…Previous studies demonstrated that ␣ D ␤ 2 is capable of binding vascular cell adhesion molecule 1 (VCAM-1) 6,7 and intercellular adhesion molecule 3 (ICAM-3). 1 VCAM-1 is present on endothelial cells and, thus, clearly absent from the extravascular compartment in which formation of foam cells occurs. ICAM-3 is present on lymphocytes that are detectable in atherosclerotic lesions (for a review, see Getz 8 ).…”

On the potential involvement of CD11d in co-stimulating the production of interferon- by natural killer cells upon interaction with neutrophils via intercellular adhesion molecule-3

“…Since CD11a and DC-SIGN do not appear to interact with ICAM-3 (Figures 1 and 2), we subsequently evaluated whether CD11d, known to show a preferential binding to ICAM-3, 8 could instead function as ICAM-3 counterreceptor in our system. Because of the absence of commercially available Abs displaying CD11d blocking properties, we performed confocal microscopy studies and found a strong constitutive expression of CD11d by slanDC and NK cells, while neutrophils were nearly negative ( Figure 3A).…”