Chitinases in Pneumocystis carinii pneumonia

Pneumocystis pneumonia remains an important complication of immune suppression. The cell wall of Pneumocystis has been demonstrated to potently stimulate host inflammatory responses, with most studies focusing on β-glucan components of the Pneumocystis cell wall. In the current study, we have elaborated the potential role of chitins and chitinases in Pneumocystis pneumonia. We demonstrated differential host mammalian chitinase expression during Pneumocystis pneumonia. We further characterized a chitin synthase gene in Pneumocystis carinii termed Pcchs5, a gene with considerable homolog to the fungal chitin biosynthesis protein Chs5. We also observed the impact of chitinase digestion on Pneumocystis-induced host inflammatory responses by measuring TNFα release and mammalian chitinase expression by cultured lung epithelial and macrophage cells stimulated with Pneumocystis cell wall isolates in the presence and absence of exogenous chitinase digestion. These findings provide evidence supporting a chitin biosynthetic pathway in Pneumocystis organisms and that chitinases modulate inflammatory responses in lung cells. We further demonstrate lung expression of chitinase molecules during Pneumocystis pneumonia.     

Experimental Pneumocystis carinii pneumonia in the ferret.

Pneumocystis carinii pneumonia (PCP) was provoked in the ferret, Mustela pulorius furo, by immunosuppression with daily long-term administration of cortisone acetate, 10-20 mg/kg subcutaneously for 9 to 10 weeks, Microscopically P. carinii was observed in the lungs of all 11 treated animals: mild to moderate in five and extensive disease in six. The histopathological features of PCP in the ferret included interstitial pneumonitis, scant mononuclear cell alveolitis, with abundant cysts and trophozoites visible in a focal distribution. There were few neutrophils present. Electron microscopy showed large numbers of both cysts and trophozoites in close association with type I cells. No bacterial pathogens were isolated from the lungs of immunosuppressed animals but an unexplained eosinophilic enteritis was present in treated animals. P carinii pneumonia developed without significant body weight loss during corticosteroid administration, unlike previously described studies using corticosteroid-treated rodents. Ferrets thus appear to be a ''steroid resistant'' animal, like man, and therefore a more suitable model for immunological studies of host response to PCP than rodents. This new model also has practical advantages over previously described animal models of PCP, including larger lung and airway size.     

Experimental Pneumocystis carinii pneumonia in the ferret

Pneumocystis carinii pneumonia (PCP) was provoked in the ferret, Mustela pulorius furo, by immunosuppression with daily long-term administration of cortisone acetate, 10-20 mg/kg subcutaneously for 9 to 10 weeks, Microscopically P. carinii was observed in the lungs of all 11 treated animals: mild to moderate in five and extensive disease in six. The histopathological features of PCP in the ferret included interstitial pneumonitis, scant mononuclear cell alveolitis, with abundant cysts and trophozoites visible in a focal distribution. There were few neutrophils present. Electron microscopy showed large numbers of both cysts and trophozoites in close association with type I cells. No bacterial pathogens were isolated from the lungs of immunosuppressed animals but an unexplained eosinophilic enteritis was present in treated animals. P carinii pneumonia developed without significant body weight loss during corticosteroid administration, unlike previously described studies using corticosteroid-treated rodents. Ferrets thus appear to be a 'steroid resistant' animal, like man, and therefore a more suitable model for immunological studies of host response to PCP than rodents. This new model also has practical advantages over previously described animal models of PCP, including larger lung and airway size.     

Pneumocystis carinii pneumonia after renal transplantation

Being immuno-suppressed, renal allograft recipients are at increased risk of contracting various infectious complications. Pneumocystis carinii pneumonia (PCP) is one of the important opportunistic infection causing high morbidity and mortality in these patients. Majority of studies has reported the occurrence of PCP during 6 months to one year after renal transplantation. This communication describes occurrence of PCP in five renal allograft recipients 10 weeks to 72 months after transplantation. In view of elusive presentation, strong clinical and radiological suspicion followed by direct demonstration of the organisms is essential for early diagnosis and prompt treatment. These observations also indicate that PCP is an emerging opportunistic infection in immuno-compromised patients in tropical countries.     

Granulomatous Pneumocystis carinii pneumonia mimicking tuberculosis

A 62-year-old man with untreated, well-differentiated lymphocytic lymphoma, presenting with progressive dyspnea, was found on open lung biopsy to have multiple necrotizing granulomas that on frozen section were initially called tuberculosis. Routine Grocott methenamine-silver stain showed these to contain Pneumocystis carinii organisms. A review of the literature shows that this is an unusual histologic presentation that can occur in a wide variety of immunosuppressed states, including the acquired immunodeficiency syndrome. The histologic similarities to tuberculous infection are stressed to increase the awareness of possible misdiagnosis that could result in delayed or inappropriate therapy.     

Pneumocystis carinii pneumonia: a light microscopical and ultrastructural study.

A case of Pneumocystis carinii pneumonia developing a patient with treated diffuse lymphocytic lymphoma is described. The electron microscopic features and life cycle of the organism are illustrated. The patient died twenty-four hours after the biopsy had been taken. Septrin appeared to have affected the trophozoite stage. Pneumocystis carinii appears to induce interstitial pulmonary oedema and fibrosis. A discussion of the role of electron microscopy in early diagnosis of the disease is presented.     

Improved rat model for studying Pneumocystis carinii pneumonia.

Sprague-Dawley rats treated for 8 weeks with cortisone acetate (25 mg per rat twice weekly) were immunosuppressed to variable degrees. A total of 55% lost over 12% of their initial body weight, had cortisol concentrations in serum more than five times greater than those of the controls, and had markedly depressed ratios of helper to non-helper T cells, in both the spleen and peripheral blood. Animals that gained weight during immunosuppression had cortisol concentrations in serum only three times higher than those of the controls, had normal ratios of helper to non-helper T cells in the spleen, and had only modestly reduced T-cell ratios in peripheral blood. The degree of Pneumocystis pneumonia was evaluated in impression smears and sections of lungs taken from immunosuppressed rats. Pneumocystis infections were more severe in the rats that showed the greatest weight loss. Weight change during immunosuppression may therefore be used as a reliable means for predicting the degree of Pneumocystis infection in living rats. This protocol allows the selection of uniformly infected rats for studies assessing drug therapy of Pneumocystis pneumonia.     

Experimental corticosteroid induction of Pneumocystis carinii pneumonia in piglets.

Animal models of Pneumocystis carinii (Pc) pneumonia (PCP) play a central role in research on the Pc microorganism itself and the disease, especially the pathogenesis and the host defence. The classic rat model with corticosteroid-induced reactivation of a latent infection has been most widely used. In our search for alternative non-rodent models, six 31/2-week-old piglets were injected intramuscularly with methylprednisolone acetate, at 18 mg/kg body weight, once a week for 6 weeks. Six littermate piglets constituted the control group. The principals showed a markedly lower growth rate than the controls. Furthermore, they developed "moon face" and "pot belly", snoring sounds while eating, and pronounced respiratory distress during handling. Significant changes in haematological parameters, including lymphopenia, were observed in the principal group. The Pc antibody titres of the controls increased to high levels, whereas the principals were all low-titred or seronegative for Pc at the last blood sampling. At necropsy, the mean body weight of the principals was about half that of the controls. In addition, they had an extreme reduction of the thymus together with dark red consolidations of the frontal lung lobes and/or atelectatic looking diaphragmatic lobes. Histopathologically, there was a focal interstitial pneumonia. Alveolar walls and interstitia had mononuclear cell infiltrations and the alveolar lumina were occluded by foamy acidophilic honeycomb material with a varying number of Pc cysts. The reduced body weight, the thymus involution, and the lymphopenia, together with the reduced levels of specific Pc antibodies and the histomorphology of the PCP, were consistent parameters of the principal group and comparable to the findings of the classic rat model. Thus, the present study is the first to describe that prolonged administration of high doses of methylprednisolone acetate can induce PCP in piglets.     

The pathology of treated Pneumocystis carinii pneumonia

Post-mortem examinations were conducted in 28 patients with the acquired immune deficiency syndrome (AIDS) and biopsy-proven Pneumocystis carinii pneumonia (PCP) who had been treated with trimethoprim-sulfamethoxazole (Bactrim, intravenous infusion [Roche]) and/or pentamidine isethionate. According to the evolution of the pulmonary process, the cases were classified into three groups. Group I ("fulminant" PCP) was composed of eight patients who died during the first week of the disease. Although treatment had eradicated most of the organisms, one third of the alveolar space volume, on the average, was filled by foamy exudates characteristic of PCP. This accounted for the respiratory insufficiency and death of these patients. Group II ("nonresolving" PCP) was comprised of nine patients who died within eight days and 2 months of diagnosis. PCP was less severe than in group I, but fatal respiratory insufficiency was the result of fibroblastic organization of the intraalveolar exudates (fibrosing alveolitis). In seven of the nine patients (78%), the latter resulted from oxygen toxicity; in the remaining two patients (22%) PCP, per se, was the original stimulus for the fibrosis. Patients in group II also had a high incidence of thromboembolic pulmonary lesions. Group III ("cured" PCP) was composed of 11 patients who responded dramatically well to therapy but died months or years later of other manifestations of AIDS. In group III patients, the roentgenographic picture at diagnosis was consistently less severe than in groups I and II.