Role of macrophage scavenger receptors in hepatic granuloma formation in mice

In mice homozygous for the gene mutation for type I and type II macrophage scavenger receptors (MSR-A), MSR-A(-/-), the formation of hepatic granuloma s caused by a single intravenous injection of heat-killed Corynebacterium p arvum was delayed significantly for 10 days after injection, compared with granuloma formation in wild-type (MSR-A(+/+)) mice. In the early stage of g ranuloma formation, numbers of macrophages and their precursor cells were s ignificantly reduced in MSR-A(-/-) mice compared with MSR-A(+/+) mice. In c ontrast to MSR-A(+/+) mice, no expression of monocyte chemoattractant prote in-1, tumor necrosis factor-alpha, and interferon-gamma mRNA was observed i n. MSR-A(-/-) mice by 3 days after injection. Also in MSR-A(-/-) mice, upta ke of C. parvum by Kupffer cells and monocyte-derived macrophages In the ea rly stage of granuloma formation was lower and elimination of C. parvum fro m the liver was slower than in MSR-A(+/+) mice, In the livers of MSR-A(+/+) mice, macrophages and sinusoidal endothelial cells possessed MSR-A, but th is was not seen in the livers of MSR-A(-/-) mice. In both MSR-A(-/-) and MS R-A(+/+) mice, expression of other scavenger receptors was demonstrated. Th ese data suggest that MSR-A deficiency impairs the uptake and elimination o f C. parvum by macrophages and delays hepatic granuloma formation, particul arly in the early stage.