Phosphatidylinositol-anchored molecules and inducible lipopolysaccharide binding sites of human and mouse bone marrow cells.
We have previously established that lipopolysaccharide (LPS) induces the expression of new specific LPS-binding sites (LpsR) in mouse bone marrow cells (BMC). We now show that exposure of human BMC to LPS elicits the production of both CD14 molecules (detectable with monoclonal antibody My4) and LpsR (detectable with fluorescein isothiocyanate-LPS). Pretreatment of stimulated human BMC with My4 inhibited the binding of fluorescein isothiocyanate-LPS. The stimulation of human BMC, but not mouse BMC, required the presence of serum. Other characteristics of mouse and human BMC examined were very similar. Their inducible LpsR interacted with the lipid moieties of LPS and Leishmania donovani lipophosphoglycan and with a soluble preparation of peptidoglycan. Moreover, mouse and human LpsR were susceptible to treatment with a phosphatidylinositol-specific phospholipase C (PI-PLC), thus suggesting that both are PI-anchored CD14 molecules. Neither LpsR appeared able to interact with a synthetic LPS antagonist (compound PPDm2) structurally related to the lipid region of LPS. However, PPDm2 blocked LPS-induced expression of LpsR in both BMC. Furthermore, in both species, pretreatment of BMC with PI-PLC did not prevent the cells from expressing LpsR in response to LPS. The results support the hypothesis that the elicited LpsR of mouse and human BMC is an inducible form of CD14, whereas the putative "signaling LPS receptor" of these cells is not CD14 or any other PI-anchored molecule.
Pedron
T
T
Unité d'Immunophysiologie Moléculaire, URA-359 du Centre National de la Recherche Scientifique, Institut Pasteur, Paris, France.
Girard
R
R
Turco
S J
SJ
Chaby
R
R
D000209:Acute-Phase Proteins; D000818:Animals; D001665:Binding Sites; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D006017:Glycolipids / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007893:Leishmania donovani; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology; D008562:Membrane Glycoproteins; D051379:Mice; D008809:Mice, Inbred C3H; D008875:Middle Aged; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000378:metabolism*; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D012475:Salmonella; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D006017:Glycolipids; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases; D000099231:Lipopolysaccharide-Binding Protein