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 could impact atherosclerosis and inflammatory processes. To define the function 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 (lyso-bSR-A). bSR-A mRNA was present in cultured peritoneal macrophages of transgenic mice and tissues that contain significant macrophages including spleen, lung, and ileum. Functional overexpression of SR-A was demonstrated in peritoneal macrophages both by augmented cholesterol ester deposition in response to AcLDL and enhanced adhesion in transgenic mice compared with nontransgenic littermates. To determine whether macrophage-specific expression of bSR-A regulated inflammatory responses, granulomas were generated by subcutaneous injection of carrageenan. Granuloma size was significantly increased 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 larger granulomas in lyso-bSR-A transgenic mice were only associated with an increase in unesterified cholesterol, and not cholesterol esters. Furthermore, granulomas from transgenic mice had an increase in the number of macrophages within the tissue.Therefore, macrophage expression of bSR-A increased presence of this cell type in granulomas without enhancing the deposition of cholesterol esters, consistent with a role of the adhesive property of the protein.
Daugherty
A
A
Gill Heart Institute, Atherosclerosis Research Group, Division of Cardiovascular Medicine, University of Kentucky, L543 KY Clinic, Lexington, KY 40536-0284, USA. adaugh@pop.uky.edu
Kosswig
N
N
Cornicelli
J A
JA
Whitman
S C
SC
Wolle
S
S
Rateri
D L
DL
D000818:Animals; D002351:Carrageenan / Q000008:administration & dosage; D002784:Cholesterol / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression; D006099:Granuloma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000503:physiopathology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009113:Muramidase / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B
D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; C032629:acetyl-LDL; D002351:Carrageenan; D002784:Cholesterol; D009113:Muramidase