Scavenger Receptor Expression in Macrophages Challenged with Porphyromonas gingivalis

Objectives: It has been suggested that chronic infections such as periodontal disease impact atherosclerotic cardiovascular disease.  We and others have reported that Porphyromonas gingivalis, a bacterium closely associated with chronic periodontal disease, accelerates atherosclerosis in hyperlipidemic mice.  Early atherosclerotic lesions in humans are characterized by accumulation of foam cells, cholesterol-engorged macrophages.  Murine macrophages cultured with P. gingivalis in vitro can be seen to accumulate exogenously provided LDL taking on the foam cell phenotype.  Macrophage lipid accumulation is mediated by scavenger receptors (SRs).  To date, SR expression on cells challenged with P. gingivalis is poorly defined.  Our objective was to begin to characterize SR expression on macrophages cultured with P. gingivalis.  Methods: We used QRT-PCR and FACS to explore relative expression of SRs by thioglycolate-induced murine peritoneal macrophages cultured with P. gingivalis in vitro.  Results: QRT-PCR identified that P. gingivalis challenge of murine macrophages up-regulated expression of msr1 (scavenger receptor A; SR-A) while stimulating the down-regulation of cd36.  SR-A protein was observed to be significantly enhanced on the surface of macrophages in response to P. gingivalis challenge, while CD36 was significantly decreased, as compared with unchallenged cells by FACS.  Purified P. gingivalis capsular polysaccharide influenced the expression of macrophage SRs similar to whole bacteria.  Incubation with LDL did not affect surface expression of SR-A, but was seen to attenuate the P. gingivalis-induced decrease in CD36 on challenged macrophages.  Conclusion: The observed modulations of SR expression by murine macrophages incubated with P. gingivalis suggest a mechanism that could explain predisposition of these pathogen-challenged macrophages to form foam cells.

PHS grant support provided by DE014774 (FCG)