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Blood, 1 January 2005, Vol. 105, No. 1, pp. 153-160. Prepublished online as a Blood First Edition Paper on August 24, 2004; DOI 10.1182/blood-2004-03-0990. This Article Full Text (PDF) All Versions of this Article: 2004-03-0990v1 105/1/153    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mandal, S. K Articles by Rao, L V Search for Related Content PubMed PubMed Citation Articles by Mandal, S. K Articles by Rao, L V Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 16, 2004 Accepted August 12, 2004 Acute Cholesterol Depletion Impairs Functional Expression of Tissue Factor in Fibroblasts Samir K Mandal, Alexei Iakhiaev, Usha R Pendurthi, and L V Rao* Biomedical Research Division, The University of Texas Health Center at Tyler, Tyler, TX, USA * Corresponding author; email: vijay.rao{at}uthct.edu. Cholesterol, in addition to providing rigidity to the fluid membrane, plays a critical role in receptor function, endocytosis, recycling and signal transduction. In the present study, we examined the effect of membrane cholesterol on functional expression of tissue factor (TF), a cellular receptor for clotting factor VIIa. Depletion of cholesterol in human fibroblasts (WI-38) with methyl--cyclodextrin reduced TF activity at the cell surface. Binding studies with radiolabeled VIIa and TF mAB revealed that reduced TF activity in cholesterol-depleted cells stems from the impairment of VIIa interaction with TF rather than the loss of TF receptors at the cell surface. Repletion of cholesterol-depleted cells with cholesterol restored TF function. Loss of caveolar structure upon cholesterol removal is not responsible for reduced TF activity. Solubilization of cellular TF in different detergents indicated that a substantial portion of TF in fibroblasts is associated with non-caveolar lipid rafts. Cholesterol depletion studies showed that the TF association with these rafts is cholesterol-dependent. Overall the data presented herein suggest that membrane cholesterol functions as a positive regulator of TF function by maintaining TF receptors, probably in non-caveolar lipid rafts, in a high affinity state for VIIa binding. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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