Neutrophil-mediated secretion and activation of matrix metalloproteinase-9 during cardiac surgery with cardiopulmonary bypass.
Cardiopulmonary bypass (CPB) induces neutrophil activation, degranulation, and a systemic inflammatory response. Matrix metalloproteinase (MMP)-9 exists in neutrophils and is released on neutrophil activation. Increased levels of MMP-9 have been observed in patients undergoing CPB. We designed the present study to determine whether MMP-9 is derived from neutrophils during CPB. Twenty-one patients undergoing elective coronary artery bypass grafting with or without CPB were included in this study. Blood was collected and analyzed for MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1. Neutrophils were also isolated and examined for MMP-9 production and mRNA expression. Plasma levels and activity of MMP-9 increased significantly 2-6 h after beginning CPB, whereas the MMP-9 levels in patients with off-pump cardiac surgery did not increase. The neutrophil content of MMP-9 and mRNA increased significantly 2 h after beginning CPB. The plasma levels of TIMP-1 increased gradually for 6 h, whereas the MMP-9/TIMP-1 ratios were increased 2-4 h after beginning CPB. The present study demonstrated that CPB causes an increase in the concentration and activity of plasma MMP-9. The corresponding increase in neutrophil MMP-9 expression and production suggests that MMP-9 is derived primarily from neutrophils and may contribute to the inflammatory response associated with CPB.
Lin
Tso-Chou
TC
*Department of Anesthesiology and †Surgery, Tri-Service General Hospital; and ‡School of Public Heath, National Defense Medical Center, National Defense University, Taipei, Taiwan, Republic of China.
Li
Chi-Yuan
CY
Tsai
Chien-Sung
CS
Ku
Chih-Hung
CH
Wu
Ching-Tang
CT
Wong
Chih-Shung
CS
Ho
Shung-Tai
ST
D000368:Aged; D000758:Anesthesia; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D047549:Coronary Artery Bypass, Off-Pump; D004789:Enzyme Activation / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000378:metabolism*; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology*; D011480:Protease Inhibitors / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D012313:RNA; D020780:Matrix Metalloproteinase 9