Elastolytic Activity in Pulmonary Lavage Fluid from Patients with Adult Respiratory-Distress Syndrome

Abstract

To test the hypothesis that adult respiratory-distress syndrome (ARDS) is related to increased activity of the proteolytic enzyme elastase released from neutrophils in the lung, we determined the differential white-cell count, the elastolytic activity, the source of elastase, and the concentration and activity of the endogenous protease inhibitor alpha-1-antiprotease (alpha-1-AP) in bronchoalveolar lavage fluid from 23 patients with ARDS and from 55 patients without this syndrome. Neutrophil predominance (> 80 per cent) was observed in 18 of 23 patients with ARDS. High elastolytic activity of neutrophil origin was found in 12 of 23 patients with ARDS (52 per cent), in none of 16 normal nonsmokers (P < 0.01), in two of 17 normal smokers, and in three of 22 patients with chronic obstructive pulmonary disease. Although there were no significant differences in alpha-1-AP concentrations, its activity was reduced in eight of nine patients with ARDS and high elastolytic activity. We conclude that in many patients with ARDS, high levels of neutrophil elastolytic activity in the lungs are associated with reduced alpha-1-AP function.

Oxygen Exposure in the Newborn Guinea Pig Lung Lavage Cell Populations, Chemotactic and Elastase Response: a Possible Relationship to Neonatal Bronchopulmonary Dysplasia

“…The objective of this study was to elucidate the nature of cellular inflammatory response in the neonatal guinea pig lung and to determine whether elaboration of proteolytic enzymes into pulmonary effluent occurs in the immature or neonatal animal in a sequence similar to that found in adult animals and man. Both the chemotactic behavior of adult pulmonary inflammatory cells and their release of proteolytic enzymes injurious to lung tissue have been reported in adult respiratory distress syndrome (19), yet to our knowledge similar studies have not been re~orted in the " neonatal animal or human infant.…”

“…Neutropenia induced with nitrogen mustard was shown to spare the lungs of oxygen-exposed adult rats to the effects described in control animals (28), suggesting that neutrophil mediated events caused these lesions in the adult animal. Lee et al (19) found elevated levels of neutrophilic elastase in the pulmonary lavage fluid of a majority of patients with adult respiratory distress syndrome, associated with increased numbers of leukocytes in pulmonary effluent in 20 of 23 patients. These workers have suggested that serine elastase proteolysis is the mechanism involved in the pathogenesis of the adult respiratory distress syndrome.…”

Pathophysiology of Acute Lung Injury and the Acute Respiratory Distress Syndrome

“…For example, much of the neutrophil elastase recovered from the injured lung is complexed to endogenous inhibitors such as a1-antitrypsin or a2-macroglobulin and is not functional. [62][63][64][65][66][67] The balance between these destructive and protective compounds seems to be important in limiting tissue damage in ALI/ARDS. 68 Other potentially injurious products released by neutrophils include platelet activating factor (PAF) and arachidonic acid metabolites such as the leukotrienes.…”

Inhibition of Neutrophil Elastase by α1-Protease Inhibitor at the Surface of Human Polymorphonuclear Neutrophils

“…There is now a growing body of evidence that HNE, like related serine proteases from primary granules, remains in large part bound to the external surface of the plasma membrane, where it cleaves biologically relevant and synthetic substrates (5). Released, free proteases become pre-eminent upon further activation and subsequent cell lysis, as in the expectorations of cystic fibrosis patients and those suffering from severe acute lung injury such as acute respiratory distress syndrome (6). However, the regulation of proteolytic activity at inflammatory sites under conditions of mild neutrophil-dependent inflammation mainly concerns membrane-bound serine proteases that are exposed at the cell surface after mobilization of their primary granules.…”