Neutrophil infiltration increases matrix metalloproteinase-9 in the ischemic brain after occlusion/reperfusion of the middle cerebral artery in rats.
Matrix metalloproteinase-9 (MMP-9) activity increases in the brain during the first day after focal ischemia and might be involved in the pathogenesis of tissue damage. We previously showed MMP-9 in the extracellular space of brain parenchyma along with neutrophil recruitment after ischemia. In the present study, we tested whether neutrophils were a direct source of enhanced MMP-9 in the ischemic brain. Neutrophil infiltration was prevented either by injecting an antibody against ICAM-1, which abrogates neutrophil adhesion to the endothelial vessel wall, or by inducing neutropenia. One-hour intraluminal middle cerebral artery occlusion with reperfusion was induced, and studies were performed at 24 hours. Circulating neutrophils expressed 95-kDa MMP-9 and dimers, and infiltrated neutrophils stained positive for MMP-9. The expression of MMP-9 (mainly 95-kDa proform and dimers and, to a lesser extent, 88-kDa form) increased in brain after ischemia/reperfusion. Treatments preventing neutrophil infiltration failed to preclude the ischemia-induced increase in 88-kDa MMP-9 form and gelatinase activity in neurons and blood vessels. However, these treatments prevented the major increase in 95-kDa MMP-9 form and dimers. We conclude that neutrophil infiltration highly contributes to enhanced MMP-9 in the ischemic brain by releasing MMP-9 proform, which might participate in the tissular inflammatory reaction.
Justicia
Carles
C
Departament de Farmacologia i Toxicologia, IIBB-CSIC, Barcelona, Spain.
Panés
Julián
J
Solé
Sònia
S
Cervera
Alvaro
A
Deulofeu
Ramon
R
Chamorro
Angel
A
Planas
Anna M
AM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002465:Cell Movement / Q000276:immunology*; D019281:Dimerization; D018093:Gelatinases / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000276:immunology* / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology; D009503:Neutropenia / Q000201:enzymology / Q000276:immunology; D009504:Neutrophils / Q000166:cytology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9