Effects of depletion of neutrophils or macrophages on the inflammatory response induced by metalloelastase (MMP-12) in mice airways.
Macrophage elastase (recombinant human matrix metalloproteinase-12, rhMMP-12), was instilled in mouse airways, inducing an early inflammatory response characterized by neutrophil recruitment and cytokine release in the bronchoalveolar lavage (BAL) fluids, followed by a delayed macrophage recruitment. We investigated the role played by alveolar macrophages and neutrophils in the delayed macrophage influx induced by rhMMP-12 (8 x 10(-3) U/mouse) in A/J mice. Mice depleted of circulating neutrophils, using a cytotoxic antibody, did not present an increase in neutrophil numbers in bronchoalveolar lavage fluids, 4 h and 24 h after rhMMP-12 instillation but the macrophage recruitment was not modified as compared to control mice at 7 days. Similar results were obtained using mice when the gene for neutrophil elastase was knocked out. Intranasal instillation of clodronate liposomes, 72 h prior to rhMMP-12 instillation, induced macrophage depletion which did not modify the macrophage recruitment at 7 days. Moreover, the stimulation of mouse macrophages by rhMMP-12 did not elicit the release of cytokines in culture supernatants. These results indicate that resident alveolar macrophages and recruited neutrophils do not play a role in the delayed macrophage recruitment induced by rhMMP-12.
Nénan
Soazig
S
INSERM U620, University of Rennes 1, Rennes, France.
Boichot
Elisabeth
E
Planquois
Jean-Michel
JM
Berna
Patrick
P
Hitier
Simon
S
Bénard
Tsiala
T
Lagente
Vincent
V
Bertrand
Claude P
CP
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004002:Clodronic Acid / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D019272:Leukocyte Elastase / Q000235:genetics; D008081:Liposomes; D016676:Macrophages, Alveolar / Q000378:metabolism*; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism*
D016207:Cytokines; D008081:Liposomes; D004002:Clodronic Acid; D019272:Leukocyte Elastase; D053508:Matrix Metalloproteinase 12