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 manner in which the interaction between P. carinii organisms and AECs results in clinical pneumonia has not been explored. To investigate this interaction in vitro, we established a culture system using rat P. carinii 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, we demonstrated that P. carinii bound to AECs in a dose-dependent manner. During P. carinii-AEC interaction, both the AECs and the P. carinii organisms remained metabolically active. Immunofluorescent staining demonstrated 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 barrier function, transepithelial resistance across AEC monolayers was measured during interaction with organisms. Culture with P. carinii did not result in loss of AEC barrier function but in fact increased AEC transepithelial resistance in a dose- and time-dependent manner. We conclude that the direct interaction of P. carinii with AECs does not disrupt AEC metabolic, structural, or barrier function. Therefore, we speculate that additional inflammatory cells and/or their signals are required to induce the epithelial derangements characteristic of P. carinii pneumonia.
Beck
J M
JM
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
Preston
A M
AM
Wagner
J G
JG
Wilcoxen
S E
SE
Hossler
P
P
Meshnick
S R
SR
Paine
R
R
D000818:Animals; D001422:Bacterial Adhesion; D015820:Cadherins / Q000096:biosynthesis; D002470:Cell Survival; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000382:microbiology* / Q000502:physiology*; D007633:Keratins / Q000096:biosynthesis; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000096:biosynthesis; D062793:Occludin; D011010:Pneumocystis / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000382:microbiology* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D015820:Cadherins; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D007633:Keratins