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In this report, we show that apolipoprotein E (apoE)-CD16 double knockout (DKO; apoE-CD16 DKO) mice have reduced atherosclerotic lesions compared with apoE knockout mice. In vivo and in vitro foam cell analyses showed apoE-CD16 DKO macrophages accumulated less neutral lipids. Reduced foam cell formation in apoE-CD16 DKO mice is not due to change in expression of CD36, SR-A, and LOX-1. This led to a hypothesis that CD16 may have scavenger receptor activity. We presented evidence that a soluble form of recombinant mouse CD16 (sCD16) bound to malondialdehyde-modified low-density lipoprotein (MDALDL), and this binding is blocked by molar excess of MDA- modified BSA and anti-MDA mAbs, suggesting CD16 specifically recognizes MDA epitopes. Interestingly, sCD16 inhibited MDALDL binding to macrophage cell line, as well as soluble forms of recombinant mouse CD36, SR-A, and LOX-1, indicating CD16 can cross-block MDALDL binding to other scavenger receptors. Anti-CD16 mAb inhibited immune complex binding to sCD16, whereas it partially inhibited MDALDL binding to sCD16, suggesting MDALDL binding site may be in close proximity to the immune complex binding site in CD16. Loss of CD16 expression resulted in reduced levels of MDALDL-induced proinflammatory cytokine expression. Finally, CD16-deficient macrophages showed reduced MDALDL-induced Syk phosphorylation. Collectively, our findings suggest scavenger receptor activity of CD16 may, in part, contribute to the progression of atherosclerosis.<\/jats:p>","DOI":"10.4049\/jimmunol.1303075","type":"journal-article","created":{"date-parts":[[2014,7,19]],"date-time":"2014-07-19T03:52:26Z","timestamp":1405741946000},"page":"2483-2495","source":"Crossref","is-referenced-by-count":24,"title":["Scavenger Receptor Function of Mouse Fc\u03b3 Receptor III Contributes to Progression of Atherosclerosis in Apolipoprotein E Hyperlipidemic Mice"],"prefix":"10.1093","volume":"193","author":[{"given":"Xinmei","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"},{"name":"Vascular Medicine Institute, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang Pong","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"},{"name":"Vascular Medicine Institute, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yen-Chun","family":"Lai","sequence":"additional","affiliation":[{"name":"Vascular Medicine Institute, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jodi K","family":"Craigo","sequence":"additional","affiliation":[{"name":"Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"},{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pruthvi S","family":"Nagilla","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"},{"name":"Vascular Medicine Institute, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pooja","family":"Raghani","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"},{"name":"Summer Undergraduate Research Program, University of Pittsburgh , Pittsburgh, PA 15261"},{"name":"Arizona State University , Tempe, AZ 85287"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanmugam","family":"Nagarajan","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"},{"name":"Vascular Medicine Institute, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"},{"name":"Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,9,1]]},"reference":[{"key":"2025030707325704300_r1","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1172\/JCI114271","article-title":"Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man","volume":"84","author":"Yl\u00e4-Herttuala","year":"1989","journal-title":"J. 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