title: Regulation of CRIg expression and phagocytosis in human macrophages by arachidonate, dexamethasone, and cytokines.
abstract: Although the importance of the macrophage complement receptor immunoglobulin (CRIg) in the phagocytosis of complement opsonized bacteria and in inflammation has been established, the regulation of CRIg expression remains undefined. Because cellular activation during inflammation leads to the release of arachidonate, a stimulator of leukocyte function, we sought to determine whether arachidonate regulates CRIg expression. Adding arachidonate to maturing human macrophages and to prematured CRIg(+) macrophages caused a significant decrease in the expression of cell-surface CRIg and CRIg mRNA. This effect was independent of the metabolism of arachidonate via the cyclooxygenase and lipoxygenase pathways, because it was not inhibited by the nonsteroidal anti-inflammatory drugs indomethacin and nordihydroguaiaretic acid. Studies with specific pharmacological inhibitors of arachidonate-mediated signaling pathways showed that protein kinase C was involved. Administration of dexamethasone to macrophages caused an increase in CRIg expression. Studies with proinflammatory and immunosuppressive cytokines showed that IL-10 increased, but interferon-γ, IL-4, and transforming growth factor-β1 decreased CRIg expression on macrophages. This down- and up-regulation of CRIg expression was reflected in a decrease and increase, respectively, in the phagocytosis of complement opsonized Candida albicans. These data suggest that a unique inflammatory mediator network regulates CRIg expression and point to a mechanism by which arachidonate and dexamethasone have reciprocal effects on inflammation.
authors: Department of Immunopathology, South Australia Pathology, Women's and Children's Hospital Campus, North Adelaide, Australia. nick.gorgani@adelaide.edu.au
authors: Nick N
authors: NN
authors: Gorgani
authors: Umaporn
authors: U
authors: Thathaisong
authors: Violet R S
authors: VR
authors: Mukaro
authors: Ornnuthchar
authors: O
authors: Poungpair
authors: Amanda
authors: A
authors: Tirimacco
authors: Charles S T
authors: CS
authors: Hii
authors: Antonio
authors: A
authors: Ferrante
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology*; D002176:Candida albicans / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008084:Lipoxygenase / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017463:Receptors, Complement 3b / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C509991:CR1 protein, human; D016207:Cytokines; D012333:RNA, Messenger; D017463:Receptors, Complement 3b; D016718:Arachidonic Acid; D003907:Dexamethasone; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases