| MEMBRANE CHOLESTEROL MODULATES THE FLUID SHEAR STRESS RESPONSE OF POLYMORPHONUCLEAR LEUKOCYTES VIA ITS EFFECTS ON MEMBRANE FLUIDITY. | |
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MedLine Citation:
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PMID: 21525434 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Continuous exposure of polymorphonuclear leukocytes (PMNLs) to circulatory hemodynamics points to fluid flow as a biophysical regulator of their activity. Specifically, fluid flow-derived shear stresses deactivate leukocytes via actions on the conformational activities of proteins on the cell surface. Because membrane properties affect activities of membrane-bound proteins, we hypothesized that changes in the physical properties of cell membranes influence PMNL sensitivity to fluid shear stress. For this purpose, we modified PMNL membranes and showed that the cellular mechanosensitivity to shear was impaired whether we increased, reduced, or disrupted the organization of cholesterol within the lipid bilayer. Notably, PMNLs with enriched membrane cholesterol exhibited attenuated pseudopod retraction responses to shear that were recovered by select concentrations of benzyl alcohol (a membrane fluidizer). In fact, PMNL responses to shear positively correlated (R(2) = 0.96; p < 0.0001) with cholesterol-related membrane fluidity. Moreover, in low-density lipoprotein receptor-deficient (LDLr(-/-)) mice fed a high fat diet (a hypercholesterolemia model), PMNL shear-responses correlated (R(2) = 0.5; p < 0.01) with blood concentrations of unesterified (i.e. free) cholesterol. In this regard, the shear-responses of PMNLs gradually diminished and eventually reversed as free cholesterol levels in blood increased during 8-week high fat dieting. Collectively, our results provided evidence that cholesterol is an important component of the PMNL mechanotransducing capacity and elevated membrane cholesterol impairs PMNL shear-responses at least partially through its impact on membrane fluidity. This cholesterol-linked perturbation may contribute to dys-regulated PMNL activity (e.g. chronic inflammation) related to hypercholesterolemia and causal for cardiovascular pathologies (e.g., atherosclerosis). |
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Authors:
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Xiaoyan Zhang; Jonathan Hurng; Debra L Rateri; Alan Daugherty; Geert W Schmid-Schönbein; Hainsworth Y Shin |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-27 |
Journal Detail:
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Title: American journal of physiology. Cell physiology Volume: - ISSN: 1522-1563 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901225 Medline TA: Am J Physiol Cell Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University of Kentucky. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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