Lipopolysaccharide enhances CD11b/CD18 function but inhibits neutrophil aggregation.
Human neutrophils are primed in the presence of complexes of lipopolysaccharide (LPS) with its serum binding protein (LBP) in a manner dependent on CD14. Cellular consequences of priming include increased responsiveness, the upregulation of surface proteins including the adhesive integrin CD11b/CD18 (Mac-1), the increased binding of certain ligands to CD11b/CD18, and the concurrent shedding of the L-selectin homing receptor. Because expression of both CD11b/CD18 and L-selectin is obligatory for formyl peptide-stimulated neutrophil aggregation in vitro (Simon et al, Blood 82:1097, 1993), we have examined the consequences of bacterial endotoxin on the expression of neutrophil adhesive molecules. We observed that the exposure of neutrophils to LPS/LBP, while enhancing the surface numbers and adhesive function of CD11b/CD18 for latex particles, did not induce aggregation. In contrast, as the LPS/LBP concentration increased (ED50 = 30 ng/mL LPS/LBP), the ability of neutrophils to aggregate decreased in parallel with the shedding of L-selectin. Moreover, when L-selectin adhesive activity was blocked by treatment with Fab fragments of Dreg-200, aggregation was inhibited to an extent roughly proportional to the available L-selection. Blocking of LPS/LBP with CD14-specific monoclonal antibodies suppressed L-selectin shedding and preserved formyl peptide-stimulated aggregation. Taken together, the data suggest that inhibition of neutrophil aggregation by LPS/LBP is related to the expression of L-selectin via CD14 rather than LPS inhibition of CD11b/CD18 function during cellular stimulation.
Lynam
E B
EB
Department of Cytometry, University of New Mexico School of Medicine, Albuquerque 87131.
Simon
S I
SI
Rochon
Y P
YP
Sklar
L A
LA
D000209:Acute-Phase Proteins; D015703:Antigens, CD / Q000502:physiology; D015214:Antigens, Differentiation, Myelomonocytic / Q000502:physiology; D002352:Carrier Proteins / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology; D002449:Cell Aggregation / Q000187:drug effects; D006801:Humans; D019041:L-Selectin; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000032:analysis / Q000187:drug effects* / Q000502:physiology; D008562:Membrane Glycoproteins; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D019041:L-Selectin; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein