Attacking the multi-tiered proteolytic pathology of COPD: new insights from basic and translational studies.

摘要: Protease activity in inflammation is complex. Proteases released by cells response to infection, cytokines, or environmental triggers like cigarette smoking cause breakdown of the extracellular matrix (ECM). In chronic inflammatory diseases obstructive pulmonary disease (COPD), current findings indicate that pathology and morbidity are driven dysregulation protease activity, either through hyperactivity proteases deficiency dysfunction their antiprotease regulators. Animal studies demonstrate accuracy this hypothesis genetic pharmacologic tools. New work shows ECM destruction generates peptide fragments active on leukocytes via neutrophil macrophage chemotaxis towards collagen elastin derived peptides respectively. Such now have been isolated characterized vivo each case. Collectively, describes a biochemical circuit which leads activation local immunocytes, turn release cytokines more proteases, leading further leukocyte infiltration cyclical progression chronic. This concept well known, intrinsic protease-antiprotease hypothesis; recently analytic techniques become sensitive enough establish fundamental mechanisms hypothesis, basic clinical data implicate signaling as pathologically significant targets. review discusses targeting for with special attention COPD, covering important field; novel therapeutic strategies animal human studies; perspective successes failures agents focus potential disease.