NASA Logo, External Link
Facebook icon, External Link to NASA STI page on Facebook Twitter icon, External Link to NASA STI on Twitter YouTube icon, External Link to NASA STI Channel on YouTube RSS icon, External Link to New NASA STI RSS Feed AddThis share icon
 

Record Details

Record 38 of 442
Extracellular calcium elicits a chemokinetic response from monocytes in vitro and in vivo
Author and Affiliation:
Olszak, I. T.(Partners AIDS Research Center and MGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts 02129, United States)
Poznansky, M. C.
Evans, R. H.
Olson, D.
Kos, C.
Pollak, M. R.
Brown, E. M.
Scadden, D. T.
O'Malley, B. W. [Principal Investigator]
Abstract: 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.
Publication Date: May 01, 2000
Document ID:
20040141580
(Acquired Nov 09, 2004)
Subject Category: LIFE SCIENCES (GENERAL)
Document Type: Journal Article
Publication Information: The Journal of clinical investigation; p. 1299-305; (ISSN 0021-9738); Volume 105; 9
Publisher Information: United States
Contract/Grant/Task Num: DK41415; DK50234; HL44851
Description: In English
Distribution Limits: Unclassified; Publicly available; Unlimited
Rights: Copyright
NASA Terms: CALCIUM; IN VITRO METHODS AND TESTS; IN VIVO METHODS AND TESTS; LEUKOCYTES; MONOCYTES; ANTIGENS; DOSAGE; MICE; PHYSIOLOGICAL RESPONSES; SIGNAL TRANSMISSION; SKIN (ANATOMY)
Other Descriptors: CALCIUM/PHARMACOLOGY; CHEMOTAXIS, LEUKOCYTE; MONOCYTES/DRUG EFFECTS; RECEPTORS, CELL SURFACE/METABOLISM; ANIMALS; ANTIGENS, CD14; CALCIUM SIGNALING; CYTOSOL/METABOLISM; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMAN; MICE; RECEPTORS, CALCIUM-SENSING; RECEPTORS, CHEMOKINE/BIOSYNTHESIS; SIGNAL TRANSDUCTION; SKIN/CYTOLOGY; SUPPORT, NON-U.S. GOV'T; SUPPORT, U.S. GOV'T, P.H.S; NASA DISCIPLINE MUSCULOSKELETAL; NON-NASA CENTER
Availability Source: Other Sources
› Back to Top
NASA Logo, External Link
NASA Official: Gerald Steeman
Site Curator: STI Program
Last Modified: August 23, 2011
Contact Us