Degradation of connective tissue components by lung derived leucocytes in vitro: role of proteases and oxidants

Inflammatory leucocytes are implicated in connective tissue damage during chronic inflammatory lung disease. In an investigation of the role of leucocytes in connective tissue derangements in the lung, inflammatory leucocytes were generated in rat lungs by intratracheal instillation of inflammatory agents and retrieved by bronchoalveolar lavage. The proteolytic activities of control macrophages and of two inflammatory cell populations were compared; iodinated collagen, laminin, and fibronectin matrices were used. The inflammatory cells caused consistently and substantially more degradation of the matrices than the controls on a per cell basis. The oxidant scavengers superoxide dismutase and catalase did not inhibit matrix degradation, but alpha 1 protease inhibitor and alpha 2 macroglobulin were inhibitory. It is concluded that matrix damage in this assay is enhanced by inflammatory cells and is mediated principally by serine protease activity.