Bacterial lipopolysaccharide enhances chemoattractant-induced elastase secretion by human neutrophils.
Bacterial lipopolysaccharide (LPS) has previously been shown to enhance a number of chemoattractant-induced responses by human neutrophils. The possible role of elastase, a neutral protease with broad substrate specificity, in neutrophil-mediated vascular injury of a variety of diseases prompted us to examine a) whether or not LPS enhances the direct chemoattractant-induced secretion of elastase, b) the quantitative requirements of LPS and chemotactic factors, and c) some structural requirements of LPS for this effect. Our results show that LPS at 10 ng/ml and above, enhanced formyl-methionyl-leucyl-phenylalanine-induced neutrophil secretion of elastase, as well as secretion of myeloperoxidase and vitamin B12-binding protein. This effect was independent of cytochalasins or surface stimulation, and thus may occur during chemotactic factor stimulation in vivo. LPS also enhanced neutrophil secretory responses to the complement fragments C5a, C5a des arg, and, to a lesser degree, to leukotriene B4 and platelet-activating factor. This enhancement effect appeared to require the presence of the lipid A moiety and/or parts of the core polysaccharide but not the O-antigen portion of the LPS molecule. Our findings identify a possible LPS-dependent mechanism of neutrophil elastase-mediated tissue injury in Gram-negative infections.
Fittschen
C
C
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Sandhaus
R A
RA
Worthen
G S
GS
Henson
P M
PM
D000942:Antigens, Bacterial; D002474:Cell-Free System; D002630:Chemotactic Factors / Q000494:pharmacology*; D003182:Complement C5 / Q000031:analogs & derivatives / Q000494:pharmacology; D015936:Complement C5a; D015937:Complement C5a, des-Arginine; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D019081:O Antigens; D010196:Pancreatic Elastase / Q000378:metabolism*
D000942:Antigens, Bacterial; D002630:Chemotactic Factors; D003182:Complement C5; D015937:Complement C5a, des-Arginine; D008070:Lipopolysaccharides; D019081:O Antigens; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D010196:Pancreatic Elastase