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Cell surface receptor CD14 is necessary for lipopolysaccharide recognition but is not sufficient for ligand-specific activation of proinflammatory responses

Posted on:1998-12-12Degree:Ph.DType:Dissertation
University:Boston UniversityCandidate:Savedra, Ricardo, JrFull Text:PDF
GTID:1464390014978894Subject:Biology
Abstract/Summary:
Septic shock syndrome is initiated by the interactions of microbial products, such as bacterial lipopolysaccharide (LPS), with receptors present on phagocytes and other immunologically active cells. CD14, a glycosylphosphatidylinositol-linked protein present phagocytes on the surface of phagocytes and as a soluble proteolytic fragment in blood, is one of several receptors that bind LPS. In contrast to phagocytes, Chinese hamster ovary (CHO) and HT1080 fibrosarcoma cell lines provide a cellular background in which LPS receptors may be examined individually. Wild-type CHO and HT1080 fibrosarcoma cells, which do not express CD14, do not respond to LPS. After stable transfection of anexpression plasmid containing the human CD14 cDNA (CD14hu) into CHO and HT1080 cells, LPS-inducible translocation of the transcription factor NF-;CD14 also functions as a receptor required for activation of leukocytes by bacterial products such as peptidoglycan (PG), protein-free Staphylococcus aureus lipid extracts, fungal products, and mycobacterial lipoarabinomannan (LAM). These conclusions were based primarily on the ability of an anti-CD14 monoclonal antibody to block cellular responses to these ligands. Lipid IV...
Keywords/Search Tags:CD14, LPS
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