| Extracellular calcium elicits a chemokinetic response from monocytes in vitro and in vivo. | |
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MedLine Citation:
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PMID: 10792005 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recruitment of macrophages to sites of cell death is critical for induction of an immunologic response. Calcium concentrations in extracellular fluids vary markedly, and are particularly high at sites of injury or infection. We hypothesized that extracellular calcium participates in modulating the immune response, perhaps acting via the seven-transmembrane calcium-sensing receptor (CaR) on mature monocytes/macrophages. We observed a dose-dependent increase in monocyte chemotaxis in response to extracellular calcium or the selective allosteric CaR activator NPS R-467. In contrast, monocytes derived from mice deficient in CaR lacked the normal chemotactic response to a calcium gradient. Notably, CaR activation of monocytes bearing the receptor synergistically augmented the transmigration response of monocytes to the chemokine MCP-1 in association with increased cell-surface expression of its cognate receptor, CCR2. Conversely, stimulation of monocytes with MCP-1 or SDF-1alpha reciprocally increased CaR expression, suggesting a dual-enhancing interaction of Ca(2+) with chemokines in recruiting inflammatory cells. Subcutaneous administration in mice of Ca(2+), MCP-1, or (more potently) the combination of Ca(2+) and MCP-1, elicited an inflammatory infiltrate consisting of monocytes/macrophages. Thus extracellular calcium functions as an ionic chemokinetic agent capable of modulating the innate immune response in vivo and in vitro by direct and indirect actions on monocytic cells. Calcium deposition may be both consequence and cause of chronic inflammatory changes at sites of injury, infection, and atherosclerosis. |
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Authors:
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I T Olszak; M C Poznansky; R H Evans; D Olson; C Kos; M R Pollak; E M Brown; D T Scadden |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 105 ISSN: 0021-9738 ISO Abbreviation: J. Clin. Invest. Publication Date: 2000 May |
Date Detail:
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Created Date: 2000-05-25 Completed Date: 2000-05-25 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1299-305 Citation Subset: AIM; IM; S |
Affiliation:
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Partners AIDS Research Center and MGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts 02129, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD14 Calcium / pharmacology* Calcium Signaling Chemotaxis, Leukocyte* Cytosol / metabolism Dose-Response Relationship, Drug Humans Mice Monocytes / drug effects* Receptors, CCR2 Receptors, Calcium-Sensing Receptors, Cell Surface / metabolism* Receptors, Chemokine / biosynthesis Signal Transduction Skin / cytology |
| Grant Support | |
ID/Acronym/Agency:
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DK41415/DK/NIDDK NIH HHS; DK50234/DK/NIDDK NIH HHS; HL44851/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD14; 0/CCR2 protein, human; 0/Ccr2 protein, mouse; 0/Receptors, CCR2; 0/Receptors, Calcium-Sensing; 0/Receptors, Cell Surface; 0/Receptors, Chemokine; 7440-70-2/Calcium |
| Investigator | |
Investigator/Affiliation:
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B W O'Malley / Baylor Coll Med, Houston, TX |
| Comments/Corrections | |
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