Macrophage-specific expression of class A scavenger receptors enhances granuloma formation in the absence of increased lipid deposition

Class A scavenger receptors (SR-A) have several proposed functions that cou ld impact atherosclerosis and inflammatory processes. To define the functio n of SR-A in vivo, we created C57BL/6 transgenic mice that expressed bovine SR-A under the control of the restricted macrophage promoter, Lysozyme (ly so-bSR-A), bSR-A mRNA was present in cultured peritoneal macrophages of tra nsgenic mice and tissues that contain significant macrophages including spl een, lung, and ileum, Functional overexpression of SRA was demonstrated in peritoneal macrophages both by augmented cholesterol ester deposition in re sponse to AcLDL and enhanced adhesion in transgenic mice compared with nont ransgenic littermates. To determine whether macrophage-specific expression of bSR-A regulated inflammatory responses, granulomas were generated by sub cutaneous injection of carrageenan, Granuloma size was significantly increa sed in lyso-bSR-A transgenic mice compared with wild-type littermates [421 +/- 51 mg (n = 11) vs. 127 +/- 22 mg (n = 10), P < 0.001]. However, the lar ger granulomas in lyso-bSR-A transgenic mice were only associated with an i ncrease in unesterified cholesterol, and not cholesterol esters, Furthermor e, granulomas from transgenic mice had an increase in the number of macroph ages within the tissue.jlr Therefore, macrophage expression of bSR-A increa sed presence of this cell type in granulomas without enhancing the depositi on of cholesterol esters, consistent with a role of the adhesive property o f the protein.