AIM inhibits apoptosis of T cells and NKT cells in Corynebacterium-induced granuloma formation in mice.
Apoptosis inhibitor expressed by macrophages (AIM) inhibits apoptosis of CD4(+)CD8(+) (CD4/CD8) double-positive thymocytes, and supports the viability of these cells on the thymic selection. However, pleiotropic functions of AIM have been suggested. In this study, heat-killed Corynebacterium parvum (C. parvum) was injected into mice carrying the homozygous mutation (AIM(-/-)) and wild-type (AIM(+/+)) mice, to investigate the role of AIM in the formation of hepatic granulomas. In AIM(-/-) mice, the size and the number of hepatic granulomas were larger, and the resorption of granulomas was more delayed than in AIM(+/+) mice. The production of interleukin-12 was more prominent in AIM(-/-) mice than in AIM(+/+) mice. In the liver of AIM(+/+) mice, expression of AIM messenger ribonucleic acid (mRNA) increased after C. parvum injection. In situ hybridization demonstrated that AIM mRNA was expressed in Kupffer cells and exudate macrophages in the liver, especially in granulomas. Larger numbers of T cells and natural killer T (NKT) cells underwent apoptosis in the granulomas of AIM(-/-) mice, suggesting that AIM prevents apoptosis of NKT cells and T cells in C. parvum-induced inflammation. Recombinant AIM (rAIM) protein significantly inhibited apoptosis of NKT cells and T cells obtained from C. parvum-stimulated livers in vitro. These results indicate that AIM functions to induce resistance to apoptosis within NKT cells and T cells, and supports the host defense in granulomatous inflammation.
Kuwata
Kazuhisa
K
Department of Cellular Function, Division of Cellular and Molecular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Watanabe
Hisami
H
Jiang
Shu-Ying
SY
Yamamoto
Takashi
T
Tomiyama-Miyaji
Chikako
C
Abo
Toru
T
Miyazaki
Toru
T
Naito
Makoto
M
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D017931:DNA Primers; D005434:Flow Cytometry; D016908:Gram-Positive Bacterial Infections / Q000473:pathology; D006099:Granuloma / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D017403:In Situ Hybridization; D007378:Interleukins / Q000235:genetics; D007694:Killer Cells, Natural; D008107:Liver Diseases / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011425:Propionibacterium acnes / Q000472:pathogenicity*; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051116:Receptors, Scavenger; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
D051017:Apoptosis Regulatory Proteins; C117272:Cd5l protein, mouse; D017931:DNA Primers; D007378:Interleukins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger