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For example, cell\u2010cell and cell\u2010matrix interactions are crucial for leukocyte homing and recruitment to inflammatory sites. The discovery of the disintegrin and metalloprotease (ADAM) proteins, which have both adhesive and proteolytic activities, raised the question of their involvement in inflammatory processes. More interestingly, the presence of the RGD integrin\u2010binding sequence in the disintegrin domain of ADAM\u201015 (MDC\u201015; metar\u2010gidin) highlighted ADAM\u201015 as a protein particularly involved in cell\u2010cell interactions. These findings therefore prompted authors to investigate the roles of ADAM\u201015 in inflammatory diseases. Because of the early description of ADAM\u201015 expression in endothelial cells, work first focused on the roles of ADAM\u201015 in vascular diseases, and ADAM\u201015 was found to be associated with atherosclerosis. Other studies also pointed at ADAM\u201015 as a mediator of rheumatoid arthritis and intestinal inflammation as well as inherent angiogenesis. The roles of ADAM\u201015 in these diseases appear to involve mechanisms as different as cell\u2010cell interactions, cell\u2010extracellular matrix (ECM) interactions, and shedding activity. Here we review and discuss these recent discoveries pointing to ADAM\u201015 as a mediator of mechanisms underlying inflammation and as a possible therapeutic target for prevention of inflammatory diseases.\u2014Charrier\u2010Hisamuddin, L., Laboisse, C. L., Merlin, D. 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