a self-propagating matrix metalloprotease-9 (mmp-9) dependent cycle of chronic neutrophilic inflammation一个自动传输的矩阵metalloprotease-9(mmp-9)相关的慢性中性粒细胞炎症的循环.pdfVIP

A Self-Propagating Matrix Metalloprotease-9 (MMP-9) Dependent Cycle of Chronic Neutrophilic Inflammation 1,2 1,2 3 1 4 Xin Xu , Patricia L. Jackson , Scott Tanner , Matthew T. Hardison , Mojtaba Abdul Roda , James Edwin Blalock1,2, Amit Gaggar1,2,5* 1 Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 2 Gregory Fleming James CF Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 3 Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 4 Division of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands, 5 Pulmonary Service, Birmingham VA Medical Center, Birmingham, Alabama, United States of America Abstract Background: Chronic neutrophilic inflammation is a poorly understood feature in a variety of diseases with notable worldwide morbidity and mortality. We have recently characterized N-acetyl Pro-Gly-Pro (Ac-PGP) as an important neutrophil (PMN) chemoattractant in chronic inflammation generated from the breakdown of collagen by the actions of MMP-9. MMP-9 is present in the granules of PMNs and is differentially released during inflammation but whether Ac-PGP contributes to this ongoing proteolytic activity in chronic neutrophilic inflammation is currently unknown. Methodology/Principal Findings: Utilizing isolated primary blood PMNs from human donors, we found that Ac-PGP induces significant release of MMP-9 and concu