Proteolytic inactivation of cytokines by Pseudomonas aeruginosa.
Pseudomonas aeruginosa alkaline protease and elastase are thought to contribute to bacterial invasiveness, tissue damage, and immune suppression in animals and patients infected with the bacterium. This study examined the ability of the two proteases to inactivate a number of cytokines that mediate immune and inflammatory responses. Human recombinant gamma interferon (rIFN-gamma) and human recombinant tumor necrosis factor alpha were inactivated by both proteases. Murine rIFN-gamma was relatively resistant to alkaline protease but was inactivated by elastase, and human recombinant interleukin-1 alpha and recombinant interleukin-1 beta were resistant to the effects of both proteases. Western immunoblots suggested that cytokine inactivation by these proteases, where it occurred, required only limited proteolysis of the polypeptides. The ability of different P. aeruginosa strains to inactivate IFN-gamma appeared to require the production of both proteases for optimum activity. These results indicate that in vitro cytokine inactivation by Pseudomonas proteases is selective, requires only limited proteolysis, and in certain instances reflects the cooperative effects of both proteases.
Parmely
M
M
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City 66103.
Gale
A
A
Clabaugh
M
M
Horvat
R
R
Zhou
W W
WW
D000818:Animals; D001426:Bacterial Proteins; D001685:Biological Factors / Q000037:antagonists & inhibitors*; D016207:Cytokines; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D008666:Metalloendopeptidases / Q000494:pharmacology*; D051379:Mice; D011489:Protein Denaturation; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D001426:Bacterial Proteins; D001685:Biological Factors; D016207:Cytokines; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C038495:Pseudomonas serine proteinase; D012697:Serine Endopeptidases; D008666:Metalloendopeptidases; C043859:pseudolysin, Pseudomonas aeruginosa