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This Article Full Text Full Text (PDF) All Versions of this Article: 291/1/H473    most recent 01234.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Lloyd, K. L. Articles by Kubes, P. Search for Related Content PubMed PubMed Citation Articles by Lloyd, K. L. Articles by Kubes, P.

INNOVATIVE METHODOLOGY

GPI-linked endothelial CD14 contributes to the detection of LPS

Immunology Research Group, Department of Biophysics and Physiology, Institute of Infection, Immunity, and Inflammation, University of Calgary, Calgary, Alberta, Canada

Submitted 22 November 2005 ; accepted in final form 25 January 2006

The inflammatory endothelial response to LPS is critical to the host's surviving a gram-negative bacterial infection. In this study we investigated whether human endothelial cells express the functional coreceptor for LPS, CD14, and most importantly whether it is glycosylphosphatidylinositol (GPI) linked. We also examined whether plasma proteins could reconstitute an LPS response in CD14-inhibited endothelium. RT-PCR- and CD14-specific MAbs demonstrated CD14 expression on primary human umbilical vein endothelial cells (HUVEC) but not passaged HUVEC. The amino acid sequence of endothelial CD14 was 99% homologous to CD14 on monocytes. Endothelium responded to relatively low levels of LPS in the absence of plasma, and this was entirely dependent on CD14. Removal of GPI-linked proteins with phosphatidylinositol-phospholipase C prevented LPS detection and subsequent protein synthesis (E-selectin expression). Endothelial CD14 was sufficient to initiate functional leukocyte recruitment, an event inhibited by blocking its LPS binding epitope and also by removing CD14 from the endothelial surface. Plasma proteins restored only 30% of the LPS response in CD14-inhibited endothelium. In conclusion, our results strongly support an important role for endothelial membrane CD14 in the activation of endothelium for leukocyte recruitment.

human; human umbilical vein endothelial cells; inflammation; leukocyte recruitment; glycosylphosphatidylinositol

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