Release of Lysosomal Enzymes by Alveolar Mononuclear Cells

Abstract

THE finding that individuals severely deficient in the circulating enzyme inhibitor α₁-antitrypsin usually contract panlobular emphysema at an early age suggested that proteolytic enzymes were involved in the connective tissue destruction characteristic of pulmonary emphysema¹. This idea was strengthened by reports that intratracheal administration of the relatively nonspecific enzyme, papain, or the more specific enzymes, elastase or collagenase, led to the development of emphysema-like lesions in a variety of animal species^2,3. The origin of such proteolytic enzymes in vivo, and their mode of release has been the subject of much speculation, and two cell types, the polymorphonuclear (PMN) leukocyte and the alveolar macrophage are implicated. Evidence favouring the PMNs include their sequestration in the basilar portions of the lung in the non-diseased person, their containing large numbers of lysosomes, and the high incidence of concurrent infection (with resultant leukocyte infiltration) associated with non α₁-antitrypsin related emphysema. In addition human PMNs release approximately 25% of their lysosomal enzymes during phagocytosis of various particles such as zymosan, latex, and immune complexes⁴.