INTERACTION OF RAT PNEUMOCYSTIS-CARINII AND RAT ALVEOLAR EPITHELIAL-CELLS IN-VITRO

During Pneumocystis carinii pneumonia, P. carinii trophic forms adhere tightly to type I alveolar epithelial cells (AECs). However, the mann er in which the interaction between P. carinii organisms and AECs resu lts in clinical pneumonia has not been explored. To investigate this i nteraction in vitro, we established a culture system using rat P. cari nii and primary cultures of rat AECs. We hypothesized that binding of P. carinii to AECs would alter the metabolic, structural, and barrier functions of confluent AECs. Using fluorescently labeled P. carinii, w e demonstrated that P. carinii bound to AECs in a dose-dependent manne r. During P. carinii-AEC interaction, both the AECs and the P. carinii organisms remained metabolically active. Immunofluorescent staining d emonstrated that AEC expression of the junctional proteins E-cadherin and occludin and the structural protein cytokeratin 8 were unaffected by P. carinii binding. To evaluate the effect of P. carinii on AEC bar rier function, transepithelial resistance across AEC monolayers was me asured during interaction with organisms. Culture with P, carinii did not result in loss of AEC barrier function but in fact increased AEC t ransepithelial resistance ill a dose- and time-dependent manner. We co nclude that the direct interaction of P. carinii with AECs does not di srupt AEC metabolic, structural, or barrier function. Therefore, we sp eculate that additional inflammatory cells and/or their signals are re quired to induce the epithelial derangements characteristic of P. cari nii pneumonia.