The Role Of Apoptosis Of Lung Cells In The Pathogenesis Of Pneumocystis Pneumonia In Rats And The Expression Of Apoptosis-Related Gene Fas, Caspase-3, TNF-α, Bax

Pneumocystis pneumonia(PCP) remains an important, life-threatening opportunistic infection in immunocompromised patients. It is particularly prevalent among those with AIDS, hematologic or solid malignancies, or transplanted organs and among patients receiving chronic immunosuppressive therapies, particularly corticosteroids . The clinical syndrome of PCP has been well described in terms of presentation, diagnosis, therapeutic interventions, and clinical outcome. However, much less is known about the specific injury mechanisms and pathways contributing to respiratory impairment. To better understand the mechanisms of alveolar injury, we investigated the role of apoptosis of lung cells in the pathogenesis of PCP.Objective: To investigate the role of apoptosis of lung cells and theapoptosis-related gene Fas,caspase-3, TNF- α , Bax during pneumocystis pneumonia (PCP).Methods: Wistar rat model of PCP was established by subcutaneous injection with Dexamethasone. The level of TNF- α ,IFN-γ and sIL-2R in the bronchoalveolar lavage fluid (BALF) was detected by ELISA. pure alveolar epithelial type Ⅱ (AEC Ⅱ) cells were isolated from lung tissues using trypsin digestion and rat IgG 'panning' . Hoechst 33258 was used to detect the apoptosis of AEC Ⅱ. The apoptosis of lung cells was investigated by light, electron microscopy and terminal deoxynucleotidyltransferase-uridine nucleotide end-labeling technique on tissue sections from rat lungs and immunohistochemistry for fas,caspase-3 and Bax.Results: The level of TNF- α ,IFN-γ and sIL-2R of the BALF in PCP group washigher than Pneumocystis(?C) negative group and health control group(p<0.01). The number of apoptosis of AEC II in infected rat was signifiantly higher than that with uninfeced group(p<0.01) by Hochest stain . The number of apoptosis of lung cells in PCP was largely higher than that in PC negative group by terminal deoxynucleotidyltransferase-uridine nucleotide end-labeling technique on tissue sections.Compared with PC negative group, Bax immunoreactivity was not increased in PCP group (X2=0.14, P > 0.05).The positive rate of caspase-3 was 78.79%(26/33) in PCP group and 16.7%(2/12) in PC negative group.The former was significantly higher than the later(X2=14.45, P < 0.01).The positive rate of Fas was 60.61%(20/33) in PCP group and 8.3%(1/12) in negative rats. The former was higer than the later(X2=9.961, P <0.05).The expression of Fas and caspase-3 in PCP group had remarkably positive correlation^ =0.5641, P^O.01).Conclusion: Apoptosis of lung cells likely occurs through Fas/caspase-3depended-death receptor pathway during PCP in rats and may play an important role in the pathogenesis of the infection.