Abstract
Recent studies suggest that TNF-alpha plays a central role in host defenses during Pneumocystis carinii pneumonia. To determine whether P. carinii directly stimulates TNF-alpha secretion, rat alveolar macrophages were cultured in the presence of purified P. carinii. Whereas unstimulated alveolar macrophages released only 13.0 +/- 2.7 pg/ml of TNF-alpha into the medium, macrophages stimulated with P. carinii released 108.2 +/- 20.4 pg/ml of TNF-alpha after overnight culture (p = 0.0001). Maximal TNF-alpha release was observed after 8 h of incubation and required a P. carinii: macrophage ratio of at least 2.5:1. Autoclaved P. carinii were also able to trigger TNF-alpha release from macrophages albeit at a reduced level. In view of recent evidence that P. carinii is phylogenetically related to the fungi and contains a beta-glucan-rich cell wall, we hypothesized that TNF-alpha release might in part be mediated by this cell wall component. Preincubation of macrophages with particulate beta-glucan derived from Baker's yeast resulted in complete inhibition of TNF-alpha release in response to P. carinii. In addition, digestion of P. carinii with zymolyase, a preparation containing predominantly beta-glucanase activity, substantially reduced the ability of P. carinii to cause TNF-alpha release from macrophages. In a similar manner, macrophages incubated with P. carinii in the presence of laminariheptaose, an oligosaccharide that binds to macrophage beta-glucan receptors, also displayed decreased TNF-alpha release. Interestingly, TNF-alpha release may not be completely linked to the adherence of the organism to macrophages. Particulate beta-glucan significantly reduced P. carinii adherence to macrophages and also impaired TNF-alpha release. However, yeast mannan also significantly reduced P. carinii adherence to macrophages and also impaired TNF-alpha release. However, yeast mannan also significantly reduced P. carinii adherence but had no effect on TNF-alpha release. These data demonstrate that P. carinii can directly stimulate the secretion of TNF-alpha from alveolar macrophages and that this effect is largely mediated by beta-glucan components of the P. carinii cell wall.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
