Abstract
SR‐A mediates macrophage adhesion to modified substrates via activation of pro‐inflammatory molecules including iPLA2. In this study we examined the extent to which SR‐A mediates macrophage adhesion to glycated collagen and whether this results in secretion of pro‐inflammatory arachidonic acid (AA) metabolites and cytokines. When compared to SR‐A‐/‐ macrophages, SR‐A+/+ macrophages displayed increased spreading on glycated collagen, but not on native collagen. Additionally, enhanced macrophage adhesion to glycated collagen was effectively abolished by a SR‐A “decoy” receptor. These results demonstrate that SR‐A mediates macrophage adhesion to glycated collagen. SR‐A‐mediated macrophage adhesion to glycated collagen resulted in a 3‐fold increase in PLA2‐mediated production of AA metabolites including PGE2, PGI2, and TXA2. Maximal PG production occurred during the first 60 min and returned to basal after 24 hrs. Inhibitor of iPLA2 prevented production of AA metabolites and abolished SR‐A‐mediated adhesion to glycated collagen. In addition, relative to SR‐A‐/‐ macrophages, SR‐A+/+ macrophages plated on glycated collagen for 24 hours secreted 2.5‐fold more TNFα. Thus, SR‐A may contribute to increased inflammation during diabetes by mediating macrophage adhesion to glycated collagen and secretion of pro‐inflammatory metabolites. Support: NIH‐HLR01‐076682 and Sturgis Charitable Trust.
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