Macrophage scavenger receptor down-regulates mycobacterial cord factor-induced proinflammatory cytokine production by alveolar and hepatic macrophages. 2006

Yuriko Ozeki, and Hiroko Tsutsui, and Norifumi Kawada, and Hiroshi Suzuki, and Motoyuki Kataoka, and Tatsuhiko Kodama, and Ikuya Yano, and Kenji Kaneda, and Kazuo Kobayashi
Department of Host Defense, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. yuriozeki@med.osaka-cu.ac.jp

We aimed to reveal the regulatory function of macrophage scavenger receptor-A (MSR-A) in proinflammatory cytokine production by macrophages stimulated with mycobacterial cord factor (CF). By the culture with CF, MSR-A (+/+) alveolar macrophages and Kupffer cells produced TNF-alpha/MIP-1alpha in a time- and dose-dependent manner. However, the amounts of cytokines produced by them were much less compared to those produced by MSR-A (-/-) macrophages. Consistent with this, treatment of MSR-A (+/+) macrophages with anti-MSR-A antibody increased TNF-alpha production. Binding of CF to MSR-A was demonstrated by measuring the binding affinity. These results indicate that CF binds MSR-A, and MSR-A down-regulates TNF-alpha/MIP-1alpha production by activated macrophages, suggesting the role of this receptor in suppression of excessive inflammatory responses during mycobacterial infection.

UI MeSH Term Description Entries
D007728 Kupffer Cells Specialized phagocytic cells of the MONONUCLEAR PHAGOCYTE SYSTEM found on the luminal surface of the hepatic sinusoids. They filter bacteria and small foreign proteins out of the blood and dispose of worn out red blood cells. Kupffer Cell,Cell, Kupffer,Cells, Kupffer
D008262 Macrophage Activation The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. Activation, Macrophage,Activations, Macrophage,Macrophage Activations
D009169 Mycobacterium tuberculosis A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation. Mycobacterium tuberculosis H37Rv
D003311 Cord Factors Toxic glycolipids composed of trehalose dimycolate derivatives. They are produced by MYCOBACTERIUM TUBERCULOSIS and other species of MYCOBACTERIUM. They induce cellular dysfunction in animals. Trehalose Dimycolates,Cord Factor,Trehalose-6,6'-Dimycolate,Dimycolates, Trehalose,Factor, Cord,Factors, Cord,Trehalose 6,6' Dimycolate
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D016676 Macrophages, Alveolar Round, granular, mononuclear phagocytes found in the alveoli of the lungs. They ingest small inhaled particles resulting in degradation and presentation of the antigen to immunocompetent cells. Alveolar Macrophages,Macrophages, Pulmonary,Pulmonary Macrophages,Macrophage, Pulmonary,Pulmonary Macrophage,Alveolar Macrophage,Macrophage, Alveolar
D051117 Scavenger Receptors, Class A A family of scavenger receptors that mediate the influx of LIPIDS into MACROPHAGES and are involved in FOAM CELL formation. Macrophage Type-I Class-A Scavenger Receptor,Macrophage Type-II Class-A Scavenger Receptor,SR-A Proteins,SR-AI Protein,SR-AI-II Receptors,SR-AII Protein,Scavenger Receptor Class A Type I-II,Scavenger Receptors, Class A, Type I,Scavenger Receptors, Class A, Type I-II,Scavenger Receptors, Class A, Type II

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