Mechanisms of pulmonary injury

Considered here are recent concepts concerning pathogenetic mechanisms underlying alterations in lung tissue structure and function. Mechanisms of pulmonary injury are described and include (1) the capacity of proteolytic enzymes to induce experimental pulmonary emphysema with particular emphasis on the effects of elastases and collagenases on connective tissue components, (2) the effects on distal lung units of specific chemical toxins, and (3) the capacity of the circulating polymorphonuclear leukocyte to induce pulmonary injury by the action of lysosomal enzymes. Evidence is reviewed which indicates a predominant role for alterations in alveolar elastin as the basis for alveolar tissue destruction along with the delayed effects on lung function and morphology of proteolytic injury. Newer developments in the understanding of the functions of the alpha₁-globulin and other proteolytic enzyme inhibitors in the respiratory tract are considered. The special characteristics of cell damage induced by noxious agents such as cadmium, nitrogen dioxide, ozone, high oxygen concentrations as well as alpha-napthyl-thiourea, alloxan and paraquat are discussed. Finally, the proteolytic capacity of the polymorphonuclear leukocyte and the links between the leukocyte proteases and the activation of leukokinin and bradykinin generating systems are summarized, and their role in the tissue injury induced by antibody-antigen reactions, shock lung and nonspecific tissue damage is indicated.