title: Thermal stress induces epithelial permeability.
abstract: The mechanisms by which heat injury results in multiorgan system failure are unknown, but the presence of endotoxemia and intestinal hemorrhage suggests that changes in gut epithelial permeability may be crucial to this process. To determine whether alterations in epithelial permeability occur at physiologically relevant temperatures, heat-induced changes on epithelial barrier integrity were studied using a high-resistance clone of Madin-Darby canine kidney epithelial cells. Transepithelial electrical conductance increased when monolayers were heated above 38.3 degrees C. Early changes in conductance were completely reversible with cooling. Increased conductance was due to increased paracellular permeability because heat also induced increased mannitol permeability across the monolayers. A conditioning heat stress (42 degrees C for 90 min) altered heat-induced permeability. When cell monolayers were exposed to this conditioning stress 48 h before measurement of conductance with increasing temperatures, the conductance increase did not occur until they were heated to 39.4 degrees C compared with 38.8 degrees C in naive control cells. This conditioning treatment also conferred thermotolerance as measured by cell survival after a lethal 45.0 degrees C heat stress. There was no difference in the temperature at which conductance increased between preheated and control cells 96 h after a preconditioning heat stress. The conditioning heat stress resulted 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 temperature required to disrupt the epithelium.
authors.affiliation: Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
authors.forename: P L
authors.initials: PL
authors.lastname: Moseley
authors.forename: C
authors.initials: C
authors.lastname: Gapen
authors.forename: E S
authors.initials: ES
authors.lastname: Wallen
authors.forename: M E
authors.initials: ME
authors.lastname: Walter
authors.forename: M W
authors.initials: MW
authors.lastname: Peterson
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002460:Cell Line; D004285:Dogs; D004553:Electric Conductivity; D004848:Epithelium / Q000378:metabolism / Q000503:physiopathology; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006358:Hot Temperature; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D010539:Permeability; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D006360:Heat-Shock Proteins