Soluble CD14 in serum mediates LPS-induced increase in permeability of bovine pulmonary arterial endothelial cell monolayers in vitro.
Lipopolysaccharide (LPS) is a mediator of septic shock and acute respiratory distress syndrome (ARDS), conditions which are characterized by high-permeability pulmonary edema. LPS increases endothelial permeability both directly and indirectly via the pro-inflammatory cytokines produced by monocytes and macrophages. We investigated the role of soluble CD14 in serum in the increased endothelial permeability induced by LPS. Bovine pulmonary artery endothelial cells were grown to confluence on a microporous filter and the 125I-albumin clearance rate across the monolayer was determined. Even a high concentration of LPS (1 microgram/ml) did not increase endothelial permeability under a serum-free condition. In the presence of more than 3% normal human serum, LPS increased endothelial permeability. The presence of neutralizing anti-CD14 monoclonal antibody eliminated the serum-dependent effect of LPS. The addition of recombinant sCD14 completely replaced the requirement for serum. LPS-binding protein (LBP) did not enhance the rsCD14-mediated LPS effect, and anti-LBP antibody did not attenuate the serum-dependent LPS effect. These findings suggest that sCD14 in serum mediates the permeability-increasing effect on LPS on endothelial cells but that LBP is not necessary for this effect.
Ishii
Y
Y
Department of Pulmonary Medicine, Jichi Medical School, Tochigi, Japan.
Shuyi
W
W
Kitamura
S
S
D000209:Acute-Phase Proteins; D000818:Animals; D015703:Antigens, CD / Q000097:blood / Q000502:physiology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood / Q000502:physiology*; D001769:Blood; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002352:Carrier Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein