Chemoattractant-induced release of elastase by lipopolysaccharide (LPS)-primed neutrophils; inhibitory effect of the anti-inflammatory drug nimesulide.
Human neutrophils, pre-exposed to low concentrations (1-10 ng/ml) of bacterial LPS in the presence of 1% autologous serum, released elastase activity in response to N-formyl-met-leu-phe (fMLP). Both cell incubation with LPS without subsequent fMLP stimulus and fMLP stimulation without prior exposure to LPS failed to promote significant elastase release. Therefore, LPS primes neutrophils for the subsequent release of elastase in response to fMLP. Compared with fMLP, human recombinant C5a had a slight although not significant activity, whereas other chemoattractants such as IL-8, platelet-activating factor and leukotriene B4 were ineffective. The fMLP-induced response of LPS-primed neutrophils was susceptible to suppression by the methane-sulphonanilide anti-inflammatory drug nimesulide and RO 20-1724, which selectively inhibit cAMP-catabolizing phosphodiesterase type IV. This suggests that the elastase release by LPS-primed neutrophils is likely to be controlled by intracellular cAMP, and raises the possibility of limiting pharmacologically the elastase-mediated tissue injury during neutrophilic inflammation.
Ottonello
L
L
First Medical Clinic, Department of Internal Medicine, University of Genova Medical School, Italy.
Barbera
P
P
Dapino
P
P
Sacchetti
C
C
Dallegri
F
F
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004336:Drug Antagonism; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D013449:Sulfonamides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019272:Leukocyte Elastase; C012655:nimesulide