Respiratory epithelial permeability in complete Freund's adjuvant rat lung granulomatosis

To investigate Freund's adjuvant-induced changes in respiratory epithelial permeability, we determined the respiratory epithelium clearance of 99mTc-DTPA (RC-DTPA) in rats and the localization of horseradish peroxidase (HRP) across the lung epithelium. RC-DTPA was determined before and after intravenous injection of saline (control) or complete Freund's adjuvant (CFA). Although the respiratory epithelium was not disrupted, RC-DTPA was increased 15 min after injection of CFA and was still high after 3 d but had returned to normal after 7 d, after which it again increased and stayed high from Day 42 through Day 112. Cell number obtained by bronchoalveolar lavage increased from 15 min to 3 d after injection of CFA. Lung granulomatosis was observed 14 to 112 d after injection of CFA; changes in RC-DTPA correlated with changes in alveolar cells. HRP was present in bronchiolar intercellular spaces only in the CFA group. We conclude that (1) RC-DTPA increases in rat lung CFA granulomatosis 15 min to 3 and 42 to 112 d following injection, (2) the increase in RC-DTPA is not related to a rupture of epithelium but (3) is proportional to the cell influx into the lung, and (4) is possibly caused by the opening of tight junctions in small airways.