Role of inflammation in respiratory tract infections.
In respiratory tract infections, leukocytes are recruited to the lungs, where they help remove invading organisms through phagocytic clearance. In some instances, however, the normal inflammatory response may be as destructive as it is defensive. The neutrophils secrete a proteolytic enzyme, neutrophil elastase, which has emerged as a major culprit in the pathogenesis of inflammatory airway disease. This enzyme has been found to strip the bronchial epithelium, reduce ciliary beating, and stimulate excess mucus secretion, leading to mucus retention, bacterial proliferation, and recurrent infections. Neutrophil elastase also stimulates epithelial cell interleukin-8 secretion and produces other chemoattractant cleavage products that lead to further neutrophil recruitment. It also impairs host defenses by damaging the major opsonophagocytic receptor on the neutrophil and by weakening the efficacy of immunoglobulins. For this reason, an important goal in the treatment of respiratory tract infections should be to prevent or shorten the duration of neutrophil elastase release. A number of different approaches have been proposed or attempted in an effort to modulate the proteinase burden. These include direct inhibition of elastase and interference with the recruitment, adherence, and degranulation of neutrophils. An even more fundamental approach would start in the bone marrow, where attempts might be made to modulate or modify neutrophil precursors so as to limit the destructive potential of the mature neutrophils.
Stockley
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RA
Lung Immunobiochemical Research Laboratory, General Hospital, Birmingham, United Kingdom.
D001854:Bone Marrow Cells; D002448:Cell Adhesion; D015550:Cell Degranulation; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D019272:Leukocyte Elastase; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D011014:Pneumonia / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000276:immunology*
D007136:Immunoglobulins; D016209:Interleukin-8; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase