Metalloproteases from Pseudomonas aeruginosa degrade human RANTES, MCP-1, and ENA-78.
The gram-negative bacterium Pseudomonas aeruginosa is an opportunistic human pathogen associated with both an acute lung disease in patients with hospital-acquired pneumonia and a chronic, progressive lung disease in individuals with cystic fibrosis. A unique characteristic of this bacterium in its natural environment is the secretion of a wide variety of factors designed to ensure its growth and survival. Evidence suggests, however, that when present in the human host, these same factors may contribute to disease. In the course of studying the effect of P. aeruginosa secretory factors on airway epithelial cells, we observed that metalloproteases in bacterial-conditioned medium, as well as purified alkaline protease and elastase, degraded human RANTES, monocyte chemotactic protein-1 (MCP-1), and epithelial neutrophil-activating protein-78 (ENA-78). Under identical conditions, interleukin-8 (IL-8) was significantly more resistant to proteolysis. Degradation was accompanied by a loss of chemotactic activity. These data suggest that metalloproteases from P. aeruginosa could alter the relative amounts of critical immunomodulatory cytokines in the airway and, thus, could contribute to the pathophysiology observed in P. aeruginosa-associated lung disease.
Leidal
Kevin G
KG
Department of Internal Medicine, The VA Medical Center and The University of Iowa, Iowa City, IA 52246, USA.
Munson
Kimber L
KL
Johnson
Mark C
MC
Denning
Gerene M
GM
D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000378:metabolism*; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000502:physiology; D004492:Edetic Acid / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000031:analogs & derivatives* / Q000378:metabolism*; D045726:Metalloproteases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000276:immunology; D011994:Recombinant Proteins / Q000378:metabolism
C486263:CXCL5 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D011994:Recombinant Proteins; D004492:Edetic Acid; D045726:Metalloproteases