Production of plasminogen activator and plasminogen activator inhibitors by alveolar macrophages in control subjects and AIDS patients

Objective: To reveal a possible impairment of the plasminogen activator system in the pulmonary infections of AIDS patients. Design: To test the plasminogen activator system functionality in alveolar macrophages and bronchoalveolar lavage fluid (BALF) in control subjects and AIDS patients. Procedures were designed to detect the presence of imbalance in plasminogen activator activity and to ascertain if this imbalance is due to a direct effect of the HIV virus on macrophages or to superimposed opportunistic infection. Methods: Alveolar macrophages obtained by bronchoalveolar lavage (BAL) were either lysed with Triton X-100 or cultured for 24 h. Plasminogen activators and plasminogen activator inhibitors (PAI) were measured by chromogenic substrate assay and binding to I-125-urokinase followed by 10% sodium dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE), respectively. Results: Plasminogen activator activity in BALF and in alveolar macrophages from AIDS patients was decreased. This reduction was independent of the presence of an infectious pulmonary process. In contrast, free PAI was increased in AIDS patients with Pneumocystis carinii infection. this increase is possibly caused by a different glycosylated form of PAI-2. Conclusions: Our data support the view that the pulmonary fibrogenic response is in part secondary to an imbalance within the plasminogen activator system and provide the basis for clarifying the role of these alterations in the pathophysiology of AIDS-related pulmonary infections.