The intestinal epithelial cytoskeleton selectively constrains
lumen-to-tissue migration of neutrophils.
Hofman, Paul, Lisanne D'andrea, Denice Carnes, Sean P. Colgan, and
James L. Madara.
Division of Gastrointestinal Pathology, Departments of Pathology
and Center for Experimental Therapeutics and Reperfusion Injury,
Department of Anesthesia, Brigham and Women's Hospital and Harvard
Medical School, and the Harvard Digestive Diseases Center, Boston, MA
02115, USA
APStracts 3:0027C, 1996.
Migration of neutrophils (PMN) across polarized epithelia is
asymmetrical - basolateral-to-apical (physiologically directed)
migration is far more efficient than migration in the reverse
direction, suggesting the presence of "luminal retention
signal(s)". Following pilot observations, we used polarized
intestinal epithelial monolayers (T84) to examine whether
asymmetrical constraint of migration afforded by the epithelial
cytoskeleton, might underlie such retention signals. Rearrangement of
epithelial cortical F-actin accompanied PMN transepithelial migration
(in either direction) and was prevented by pre-loading monolayers
with the F-actin stabilizing agent phallacidin. While phallacidin
pre-loading did not influence physiologically directed PMN
transepithelial migration, such treatment greatly enhanced migration
in the reverse direction (i.e. effective loss of luminal retention
signal). BAPTA preloading also prevented epithelial cortical actin
rearrangements and selectively resulted in loss of luminal retention
signal(s). BAPTA preloading did not influence resistance or forskolin
induced Cl- secretion and phallicidin preloading did not influence
resistance or carbachol induced Cl- secretion suggesting that barrier
function and surface polarity were maintained under these conditions.
These and supplementary data suggest that epithelial actin (but not
microtubule) cytoskeletal reordering asymmetrically influences PMN
migration and underlies, at least in part, the observed signal which
biases for retention of PMN in the luminal space.
Received 27 November 1995; accepted in final form 11 January
1996.
APS Manuscript Number C706-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 January 96