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 activato r system in the pulmonary infections of AIDS patients. Design: To test the plasminogen activator system functionality in alveolar macrophage s and bronchoalveolar lavage fluid (BALF) in control subjects and AIDS patients. Procedures were designed to detect the presence of imbalanc e in plasminogen activator activity and to ascertain if this imbalance is due to a direct effect of the HIV virus on macrophages or to super imposed opportunistic infection. Methods: Alveolar macrophages obtaine d 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 bin ding to I-125-urokinase followed by 10% sodium dodecyl-sulphate polyac rylamide gel electrophoresis (SDS-PAGE), respectively. Results: Plasmi nogen activator activity in BALF and in alveolar macrophages from AIDS patients was decreased. This reduction was independent of the presenc e of an infectious pulmonary process. In contrast, free PAI was increa sed in AIDS patients with Pneumocystis carinii infection. this increas e is possibly caused by a different glycosylated form of PAI-2. Conclu sions: Our data support the view that the pulmonary fibrogenic respons e is in part secondary to an imbalance within the plasminogen activato r system and provide the basis for clarifying the role of these altera tions in the pathophysiology of AIDS-related pulmonary infections.