Cell-free pool of CD14 mediates activation of transcription factor NF-kappa B by lipopolysaccharide in human endothelial cells.

Read MA, Cordle SR, Veach RA, Carlisle CD, Hawiger J
Proc Natl Acad Sci U S A. 1993 90 (21): 9887-91

PMID: 7694295 · PMCID: PMC47677 · DOI:10.1073/pnas.90.21.9887

Lipopolysaccharide (LPS), a major envelope component of Gram-negative bacteria, is the most frequent causative agent of septic shock and disseminated intravascular coagulation. LPS activates both CD14-positive (monocytes, macrophages, polymorphonuclear leukocytes) and CD14-negative (B-cell lines, endothelial cells) cells. CD14, a 55-kDa glycosyl-phosphatidylinositol-anchored membrane protein present on mature myeloid cells, serves as a receptor for LPS in complex with a soluble (serum-derived) LPS-binding protein (LBP). In this report, we show that human umbilical vein endothelial cells (HUVEC), which do not express measurable CD14 protein, become 3000-fold more sensitive to LPS-induced activation in the presence of serum, as measured by activation of the transcription factor NF-kappa B and expression of mRNA encoding tissue factor, a procoagulant molecule. This enhanced responsiveness of HUVEC is specifically mediated by the cell-free pool of CD14 (soluble CD14, sCD14) found in serum. The role of sCD14 in HUVEC activation by LPS was established by (i) the blocking effect of monoclonal anti-CD14 antibodies which discriminate between cell-bound and sCD14, (ii) the lack of the serum-enhancing effect after immunodepletion of sCD14, and (iii) establishing a reconstituted system in which recombinant sCD14 was sufficient to enhance the effects of LPS in the absence of serum and without a requirement for LBP. Thus, this mechanism of endothelial cell activation by LPS involves a cell-free pool of sCD14 most likely shed from CD14-positive cells of the monocytic lineage.

MeSH Terms (21)

Animals Antigens, CD Antigens, Differentiation, Myelomonocytic Base Sequence Binding Sites Cell Nucleus Cells, Cultured Endothelium, Vascular Enhancer Elements, Genetic Gene Expression Humans Immunoglobulin kappa-Chains Lipopolysaccharide Receptors Lipopolysaccharides Mice Molecular Sequence Data NF-kappa B Oligodeoxyribonucleotides Recombinant Proteins RNA, Messenger Umbilical Veins

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