Dual effects of soluble CD14 on LPS priming of neutrophils.
To evaluate the effect of soluble CD14 (sCD14) on human neutrophil response to lipopolysaccharide (LPS), we developed an LPS-priming assay that measures the chemiluminescence response to N-formyl-methionyl-leucyl-phenylalanine stimulation. Priming by 1 ng/mL rough LPS occurred in the presence of either serum or recombinant LPS-binding protein (LBP) only. Priming was completely CD14-dependent because preincubation of the neutrophils with an anti-CD14 monoclonal antibody prevented priming. We hypothesize that sCD14 enhances LPS response in neutrophils, but this response is not as effective as LPS response via membrane CD14 (mCD14). In our experiments sCD14 is present in an excess compared with mCD14. Priming of neutrophils occurs with low LBP, supposedly via sCD14-LPS complexes. With high LBP, addition of sCD14 inhibited LPS-priming of neutrophils. In that case, LPS may be transported to sCD14, preventing a more effective response via mCD14. In this study we demonstrate that the effect of sCD14 on neutrophil response to LPS is a delicate balance between activation and inhibition depending on concentration of serum or LBP.
Troelstra
A
A
Eijkman-Winkler Institute, Utrecht University, The Netherlands.
Giepmans
B N
BN
Van Kessel
K P
KP
Lichenstein
H S
HS
Verhoef
J
J
Van Strijp
J A
JA
D000209:Acute-Phase Proteins; D002352:Carrier Proteins / Q000097:blood / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000502:physiology*; D008070:Lipopolysaccharides / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D012995:Solubility; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000099231:Lipopolysaccharide-Binding Protein