Complement receptor type 3 (CR3)- and Fc receptor (FcR)-mediated matrix metalloproteinase 9 (MMP-9) secretion and their intracellular signalling of bovine neutrophils.
Complement receptor type 3 (CR3)- and Fc receptor (FcR)-mediated metalloproteinase-9 (MMP-9) secretion and their intracellular signalling of bovine neutrophils were evaluated. Relative density of MMP-9 secreted by neutrophils stimulated with opsonized zymosan (OPZ, stimulant for CR3) was significantly (p < 0.05) increased when the OPZ concentration was increased from 0 to 0.4 mg/ml. Similar results were obtained for neutrophils stimulated with heat-aggregated IgG (Agg-IgG, stimulant for Fc receptor) at concentrations from 0 to 0.40 mg/ml. Preincubation of neutrophils with 1-30 nmol/L wortmannin (phosphoinositide 3-kinase inhibitor) resulted in inhibition of MMP-9 secretion induced by stimulation with OPZ and Agg-IgG in a concentration-dependent manner, 30 nmol/L wortmannin causing complete inhibition. Similarly, preincubation of neutrophils with 0-100 mumol/L genistein (tyrosine kinase inhibitor) also resulted in inhibition of OPZ- and Agg-IgG-induced MMP-9 secretion in a concentration-dependent manner, with 100 micromol/L genistein causing complete inhibition. Significant (p < 0.05) positive correlations were found between MMP-9 and luminal-dependent chemiluminescent response (LDCL) in the case of stimulation with OPZ (r = 0.754) and in the case of stimulation with Agg-IgG (r = 0.728). Our findings suggested that CR3 and FcR play a critical role in production of MMP-9 and may be regulated by intracellular signal transduction, including that by phosphoinositide 3-kinase (PI3K) and tyrosine kinase (TK).
Higuchi
H
H
Animal Health Laboratory, Faculty of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan. higuchi@rakuno.ac.jp
Ishizaka
M
M
Nagahata
H
H
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002417:Cattle / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel / Q000662:veterinary; D019833:Genistein / Q000494:pharmacology; D007074:Immunoglobulin G / Q000276:immunology; D008163:Luminescent Measurements / Q000662:veterinary; D020780:Matrix Metalloproteinase 9 / Q000276:immunology / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D018375:Neutrophil Activation / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011951:Receptors, Complement / Q000276:immunology* / Q000378:metabolism; D011961:Receptors, Fc / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D018709:Statistics, Nonparametric; D000077191:Wortmannin; D015054:Zymosan / Q000276:immunology
D000730:Androstadienes; D007074:Immunoglobulin G; D061965:Matrix Metalloproteinase Inhibitors; D047428:Protein Kinase Inhibitors; D011951:Receptors, Complement; D011961:Receptors, Fc; D015054:Zymosan; D019833:Genistein; D020780:Matrix Metalloproteinase 9; D000077191:Wortmannin