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, Kiyoshi Takahashi*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Scopus)

Abstract

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-α, and interferon-γ mRNA was observed in MSR-A-/- mice by 3 days after injection. Also in MSRA-/- 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.

Original languageEnglish
Pages (from-to)705-720
Number of pages16
JournalAmerican Journal of Pathology
Volume154
Issue number3
DOIs
Publication statusPublished - Mar 1999
Externally publishedYes

Bibliographical note

Funding Information:
Supported in part by Grants-in-Aid for scientific research from the Ministry of Education, Science, and Culture, Japan ( 08457071 and 09877048 ).

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