The aim of this study was to assess the production of uPA and TGF-β in HIV+ and immunodepressed patients with and without P.carinii. Thirty-one subjects were divided into 5 groups. Ten healthy volunteers with no past history of lung desease or symptoms suggesting viral infections in the last three months, as controls. Ten HIV+ patients, 7 without (H+PC-) and 3 with (HIV+PC+) P.carinii pneumonia (PCP). Eleven immunosuppressed patients, 8 without (IS PC-) and three with (IS PC+) PC. PA production by PBM obtained from the different groups of patients was determined by chromogenic substrate assay in cell lysates and conditioned media. Similarly to what shown with alveolar macrophages (AMs) [3] uPA activity was found mainly in cell lysates. The highest levels of PA activity were found in healthy subjects. By contrast, all HIV+ and IS patients showed a significant decrease in PA activity independently from the presence of P.carinii pulmonary infection (Table 1). However, it is interesting to notice that, although all HIV+ and IS patients showed a decreased production of uPA, in patients with PCP, uPA activity was still below normal but higher than in other patients. This increase appears to be ralated to the presence of P.carinii infection. Indeed, in a previous work [3] we observed a significant increase in uPA production by PBMs challenged in vitro with P.carinii. The decrease in uPA found in HIV+ and IS patients, may negatively affect TGF-β activation and the decrease of active TGF-β may in turn, influence virus replication since it has been demonstrated that TGF-β can suppress human HIV expression in monocyte/macrophages.
Urokinase plasminogen activator and TGF-beta production in immunosuppressed patients with and without Pneumocystis carinii
CONTINI, Carlo;
2001
Abstract
The aim of this study was to assess the production of uPA and TGF-β in HIV+ and immunodepressed patients with and without P.carinii. Thirty-one subjects were divided into 5 groups. Ten healthy volunteers with no past history of lung desease or symptoms suggesting viral infections in the last three months, as controls. Ten HIV+ patients, 7 without (H+PC-) and 3 with (HIV+PC+) P.carinii pneumonia (PCP). Eleven immunosuppressed patients, 8 without (IS PC-) and three with (IS PC+) PC. PA production by PBM obtained from the different groups of patients was determined by chromogenic substrate assay in cell lysates and conditioned media. Similarly to what shown with alveolar macrophages (AMs) [3] uPA activity was found mainly in cell lysates. The highest levels of PA activity were found in healthy subjects. By contrast, all HIV+ and IS patients showed a significant decrease in PA activity independently from the presence of P.carinii pulmonary infection (Table 1). However, it is interesting to notice that, although all HIV+ and IS patients showed a decreased production of uPA, in patients with PCP, uPA activity was still below normal but higher than in other patients. This increase appears to be ralated to the presence of P.carinii infection. Indeed, in a previous work [3] we observed a significant increase in uPA production by PBMs challenged in vitro with P.carinii. The decrease in uPA found in HIV+ and IS patients, may negatively affect TGF-β activation and the decrease of active TGF-β may in turn, influence virus replication since it has been demonstrated that TGF-β can suppress human HIV expression in monocyte/macrophages.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
