Urokinase plasminogen activator and TGF-beta production in immunosuppressed patients with and without P. Jiroveci infection.
Macrophages play a pivotal role in a host's defence against pulmonary infections. Macrophage functions are impaired in immunosuppressed (IS) patients, regardless of whether they are HIV-positive (HIV+) or -negative (HIV-). Several studies have indicated that urokinase plasminogen activator (uPA) and transforming growth factor beta (TGF-beta) are important factors in a host's defence against pulmonary pathogens. We measured uPA and TGF-beta activity in unstimulated peripheral blood monocytes (PBM) of both HIV-infected and non-infected IS patients with or without Pneumocystis jiroveci (formerly carinii) pneumonia (PCP). As previously found in alveolar macrophages (AMs), the majority of uPA activity was found in cell lysates. The highest values of uPA activity were found in control subjects. All the patients displayed a decreased production of uPA, irrespective of HIV infection. Similarly, active TGF-beta was higher in control subjects than in HIV+ and IS patients. The presence of P. jiroveci infection further lowered uPA and TGF-beta activity. Decreased TGF-beta activation might be a consequence of lower uPA production, which may, in turn, influence virus replication, since it has been demonstrated that TGF-beta can suppress human HIV expression in monocytes/macrophages. Further studies are warranted to elucidate whether the decrease in uPA and TGF-beta activity impairs a host's defence against P. jiroveci infection.
Angelici
Elena
E
Department of Clinical Medicine, University La Sapienza, Rome, Italy.
Spezzano
Massimiliano
M
Vaccari
Sergio
S
Valentini
Sara Benedetti
SB
Romani
Roberto
R
Contini
Carlo
C
Canipari
Rita
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000378:metabolism*; D018023:HIV Seronegativity / Q000502:physiology; D006679:HIV Seropositivity / Q000150:complications / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D045363:Pneumocystis carinii; D011020:Pneumonia, Pneumocystis / Q000150:complications / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; D014568:Urokinase-Type Plasminogen Activator; C489333:acetyl-lysyl-prolyl-seryl-seryl-prolyl-prolyl-glutamyl-glutamic acid amide