In the aorta ulceration and thrombosis were characteristic of plaques with a high proportion of their volume occupied by extracellular lipid, and in which there was a shift toward a preponderance of monocyte/macrophages compared with smooth muscle cells in the cap.

The expression of PECAM, ICAM-1, VCAM-1, and E-selectin was studied in 64 samples of human coronary arteries taken from 15 explanted hearts obtained within 5 min of transplantation. Normal artery (n = 12), predominantly fibrous plaques (n = 23), and plaques containing extracellular lipid (n = 26) and three segments showing recanalization channels were studied. All endothelial cells strongly and equally expressed PECAM; positive staining was used to check that artefactual denudation of the endothelial surface had not occurred. PECAM was also present in some lipid-filled macrophages. Normal arteries showed no VCAM-1 staining but focal segments of the endothelium were positive for ICAM-1 and E-selectin. ICAM-1 was strongly and constantly expressed by the endothelium over all types of plaques and in macrophages. E-selectin expression was confined to endothelial cells and occurred on the surface in 35 per cent of fibrous and 22 per cent of lipid-containing plaques. VCAM-1 staining of surface endothelium occurred in 39 per cent of fibrous and 20 per cent of lipid-containing plaques. A population of spindle-shaped cells of macrophage type (positive for EMB11 antigen) expressed VCAM-1 in lipid-containing plaques. Adventitial vessels adjacent to plaques showed endothelial expression of ICAM-1 and E-selectin. VCAM-1 staining of adventitial vessel endothelium was associated with local lymphoid aggregation. In conclusion, the expression of cell adhesion molecules is an important element in the inflammatory component of atherosclerosis and contributes to both monocyte and lymphocyte activation and recruitment from adventitial vessels and the arterial lumen.

CD98 is expressed on both hematopoietic and nonhematopoietic cells and has been implicated in a variety of different aspects of cell physiology and immunobiology. In this study, the functional interactions between CD98 and other adhesion molecules on the surface of the promonocyte line U937 are examined by means of a quantitative assay of cell aggregation. Several of the CD98 antibodies induced homotypic aggregation of these cells without affecting cellular viability or growth. Aggregation induced by CD98 antibodies could be distinguished from that induced by ␤1-integrin (CD29) ligation by lack of sensitivity to EDTA and by increased sensitivity to deoxyglucose. Aggregation induced via CD98 and CD29 could also be distinguished by the pattern of protein tyrosine phosphorylation induced. Some CD29 antibodies partially inhibited CD98-induced aggregation, and these antibodies were neither agonistic for aggregation nor inhibitors of ␤1-integrin binding to substrates. Conversely, some CD98 antibodies were potent inhibitors of CD29-induced aggregation. Antibodies to ␤2 integrins also partially inhibited CD98-induced aggregation. Unexpectedly, 2 antibodies to CD147, an immunoglobulin superfamily member whose function has remained unclear, were also potent inhibitors of both the aggregation and the protein tyrosine phosphorylation induced via CD98 ligation. The results of this study support a central role for CD98 within a multimolecular unit that regulates cell aggregation. (Blood. 2001;98:374-382)