AJP - Cell Physiology, Vol 262, Issue 6 C1403-C1410, Copyright © 1992 by American Physiological Society
Epithelial permeability factor: a serum protein that condenses actin and opens tight junctions
A. D. Marmorstein, K. H. Mortell, D. R. Ratcliffe and E. B. Cramer
Department of Anatomy and Cell Biology, State University of New York Health Science Center, Brooklyn 11203.
An epithelial permeability factor (EPF) in human serum lowered, within 1 h,
the transepithelial electrical resistance and opened the tight junctions of
a cultured kidney epithelium (Madin-Darby canine kidney) when it came in
contact with the basolateral surface of the kidney epithelium.
Size-exclusion chromatography of serum or heat-inactivated serum resolved
seven peaks of EPF activity (approximately 15, approximately 30,
approximately 45, approximately 60, approximately 120, and approximately
240 kDa and greater than 240 kDa) with 65% of the activity at approximately
45, approximately 60, and approximately 120 kDa. Heat inactivation, which
had no effect on total activity, caused a significant decrease in the
activity at 120 kDa and an equivalent rise in activity at 45 kDa. Although
acid charcoal extraction or lectin affinity chromatography did not remove
activity, EPF activity was eliminated by pepsin. Heat-inactivated serum or
fractions containing EPF had no effect on ZO-1 localization but did cause a
dose-dependent focal condensation of the perijunctional actin ring at sites
where three or more cells were in contact. These data suggest that EPF is a
protein that appears to form multimers that interact with the basolateral
surface of the epithelium and cause constriction of the cytoskeleton and an
increase in permeability at specific sites along the tight junction.
