| Stimulation of unprimed macrophages with immune complexes triggers a low output of nitric oxide by calcium-dependent neuronal nitric oxide synthase. | |
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MedLine Citation:
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PMID: 22205701 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Immune complexes comprised of IgG-opsonized pathogens, particles, or proteins are phagocytosed by macrophages through Fcγ receptors (FcγRs). Macrophages primed with IFNγ or other pro-inflammatory mediators respond to FcγR-engagement by secreting high levels of cytokines and nitric oxide (NO). We found that unprimed macrophages produced lower levels of NO, which required efficient calcium (Ca2+) flux as demonstrated by using macrophages lacking selenoprotein K (SelK), which is required for FcγR-induced Ca2+ flux. Thus, we further investigated the signaling pathways involved in low output NO and its functional significance. Evaluation of inducible, endothelial, and neuronal nitric oxide synthases (iNOS, eNOS, and nNOS) revealed that FcγR-stimulation in unprimed macrophages caused a marked Ca2+-dependent increase in both total and phosphorylated nNOS and slightly elevated levels of phosphorylated eNOS. Also activated were three MAP kinases: ERK, JNK, and p38, of which ERK activation was highly dependent on Ca2+ flux. Inhibition of ERK reduced both nNOS activation and NO secretion. Finally, transwell experiments showed that FcγR-induced NO functioned to increase the phagocytic capacity of other macrophages and required both NOS and ERK activity. The production of NO by macrophages is conventionally attributed to iNOS, but we have revealed an iNOS-independent receptor/enzyme system in unprimed macrophages that produces low output NO. Under these conditions, FcγR-engagement relies on Ca2+-dependent ERK-phosphorylation, which in turn increases nNOS, and to a lesser extent, eNOS, which combined produce low levels of NO that function to promote phagocytosis. |
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Authors:
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Zhi Huang; Fukun W Hoffmann; Jeffrey D Fay; Ann C Hashimoto; Moti L Chapagain; Pakieli H Kaufusi; Peter R Hoffmann |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-28 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University of Hawaii, United States. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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