title: [The role of the class A scavenger receptors, SR-A and MARCO, in the immune system. Part 1. The structure of receptors, their ligand binding repertoires and ability to initiate intracellular signaling].
abstract: Recognition of pathogens by innate immune cells is mediated by pattern recognition receptors (PRR), which include scavenger receptors (SR). The class A SR, SR-A/CD204 and MARCO, are characterized by the presence of collagenous and SR cysteine-rich domains in their extracellular portions. Both receptors are expressed mainly on macrophages and dendritic cells. Thanks to their ability to bind to a wide range of polyanionic ligands, the class A SR may participate in numerous functions of these cells, such as endocytosis, and adhesion to extracellular matrix and to other cells. Among SR-A ligands are oxidized lipoproteins and β-amyloid fibrils, which link SR-A to the pathogenesis of arteriosclerosis and Alzheimer's disease. Despite the demonstration of class A SR involvement in so many processes, the lack of selective ligands precluded reaching definite conclusions concerning their signaling abilities. Using specific receptor ligation with antibodies, we showed that SR-A and MARCO trigger intracellular signaling, modulating pro-inflammatory and microbicidal activities of macrophages. Surprisingly, despite similarities in structure and ligand binding repertoires, SR-A and MARCO exert opposite effects on interleukin-12 (IL-12) production in macrophages. SR-A ligation also stimulated H₂O₂ and IL-10 production, but had no effect on the release of several other cytokines. These limited effects of specific SR-A ligation contrast with generalized enhancement of immune responses observed in SR-A-deficient mice. Recent studies have revealed that many of these effects of SR-A deficiency may be caused by compensatory changes in the expression of other receptors and/or disinhibition of signal transduction from receptors belonging to the Toll/IL-1R family, rather than by the loss of the receptor function of SR-A.
authors.affiliation: Katedra i Zakład Immunologii, Uniwersytet Jagielloński, Collegium Medicum, ul. Czysta 18, 31-121 Kraków. szjozefowski@poczta.onet.pl
authors.forename: Szczepan
authors.initials: S
authors.lastname: Józefowski
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D003593:Cytoplasm / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008024:Ligands; D008074:Lipoproteins / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000737:chemistry / Q000276:immunology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D008024:Ligands; D008074:Lipoproteins; C490460:MARCO protein, human; D011971:Receptors, Immunologic; D051117:Scavenger Receptors, Class A; D016753:Interleukin-10; D018664:Interleukin-12