THERMAL-STRESS INDUCES EPITHELIAL PERMEABILITY

The mechanisms by which heat injury results in multiorgan system failu re are unknown, but the presence of endotoxemia and intestinal hemorrh age suggests that changes in gut epithelial permeability may be crucia l to this process. To determine whether alterations in epithelial perm eability occur at physiologically relevant temperatures, heat-induced changes on epithelial barrier integrity were studied using a high-resi stance clone of Madin-Darby canine kidney epithelial cells. Transepith elial electrical conductance increased when monolayers were heated abo ve 38.3 degrees C. Early changes in conductance were completely revers ible with cooling. Increased conductance was due to increased paracell ular permeability because heat also induced increased mannitol permeab ility across the monolayers. A conditioning heat stress (42 degrees C for 90 min) altered heat-induced permeability. When cell monolayers we re exposed to this conditioning stress 48 h before measurement of cond uctance with increasing temperatures, the conductance increase did not occur until they were heated to 39.4 degrees C compared with 38.8 deg rees C in naive control cells. This conditioning treatment also confer red thermotolerance as measured by cell survival after a lethal 45.0 d egrees C heat stress. There was no difference in the temperature at wh ich conductance increased between preheated and control cells 96 h aft er a preconditioning heat stress. The conditioning heat stress resulte d in accumulation of heat-shock protein (HSP) 70 in cells at 48 h, but HSP 70 returned to control levels at 96 h. These studies demonstrate that small temperature elevations increase epithelial permeability and that prior heat stress which induces HSP 70 shifts the threshold temp erature required to disrupt the epithelium.