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(American Journal of Pathology. 1999;154:705-720.)
© 1999 American Society for Investigative Pathology

Regular Articles

Role of Macrophage Scavenger Receptors in Hepatic Granuloma Formation in Mice

Sho-Ichiro Hagiwara* , Motohiro Takeya* , Hiroshi Suzuki , Tatsuhiko Kodama§ , Luc J. W. van der Laan¶ , Georg Kraal¶ , Nobuo Kitamura and Kiyoshi Takahashi*

From the Second Department of Pathology* and First Department of Surgery, Kumamoto University School of Medicine, Kumamoto, Japan; Exploratory Research Laboratory, Chugai Pharmaceutical Co. Ltd., Shizuoka, Japan; Department of Molecular Biology and Medicine, Research Center for Advanced Science and Technology,§ University of Tokyo, Tokyo, Japan; and the Department of Cell Biology,¶ Free University, Amsterdam, The Netherlands

In mice homozygous for the gene mutation for type I and type II macrophage scavenger receptors (MSR-A), MSR-A^-/-, the formation of hepatic granulomas caused by a single intravenous injection of heat-killed Corynebacterium parvum was delayed significantly for 10 days after injection, compared with granuloma formation in wild-type (MSR-A^+/+) mice. In the early stage of granuloma formation, numbers of macrophages and their precursor cells were significantly reduced in MSR-A^-/- mice compared with MSR-A^+/+ mice. In contrast to MSR-A^+/+ mice, no expression of monocyte chemoattractant protein-1, tumor necrosis factor-, and interferon- mRNA was observed in MSR-A^-/- mice by 3 days after injection. Also in MSR-A^-/- mice, uptake of C. parvum by Kupffer cells and monocyte-derived macrophages in the early stage of granuloma formation was lower and elimination of C. parvum from 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 this was not seen in the livers of MSR-A^-/- mice. In both MSR-A^-/- and MSR-A^+/+ mice, expression of other scavenger receptors was demonstrated. These data suggest that MSR-A deficiency impairs the uptake and elimination of C. parvum by macrophages and delays hepatic granuloma formation, particularly in the early stage.

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