|
|
|
|
|
|
|
||
J. Exp. Med.,
Volume 187, Number 12, June 15, 1998 1927-1940
By
From the * Department of Internal Medicine and the Immune cell migration into and through mucosal barrier sites in general and airway sites in
particular is a critical feature of immune and inflammatory responses, but the determinants of transepithelial (unlike transendothelial) immune cell traffic are poorly defined. Accordingly, we
used primary culture airway epithelial cells and peripheral blood mononuclear cells to develop a cell monolayer system that allows for apical-to-basal and basal-to-apical T cell transmigration
that can be monitored with quantitative immunofluorescence flow cytometry. In this system,
T cell adhesion and subsequent transmigration were blocked in both directions by monoclonal
antibodies (mAbs) against lymphocyte function-associated antigen 1 (LFA-1) or intercellular
adhesion molecule 1 (ICAM-1) (induced by interferon Department of Cell Biology and Physiology,
Washington University School of Medicine, St. Louis, Missouri 63110
[IFN-] treatment of epithelial cells). The total number of adherent plus transmigrated T cells was also similar in both directions, and
this pattern fit with uniform presentation of ICAM-1 along the apical and basolateral cell surfaces. However, the relative number of transmigrated to adherent T cells (i.e., the efficiency of
transmigration) was increased in the basal-to-apical relative to the apical-to-basal direction, so an additional mechanism was needed to mediate directional movement towards the apical surface. Screening for epithelial-derived 
-chemokines indicated that IFN- treatment caused selective expression of RANTES (regulated upon activation, normal T cell expressed and secreted), and the functional significance of this finding was demonstrated by inhibition of
epithelial-T cell adhesion and transepithelial migration by anti-RANTES mAbs. In addition,
we found that epithelial (but not endothelial) cells preferentially secreted RANTES through the apical cell surface thereby establishing a chemical gradient for chemotaxis across the epithelium to a site where they may be retained by high levels of RANTES and apical ICAM-1.
These patterns for epithelial presentation of ICAM-1 and secretion of RANTES appear preserved in airway epithelial tissue studied either ex vivo with expression induced by IFN-
treatment or in vivo with endogenous expression induced by inflammatory disease (i.e., asthma). Taken together, the results define how the patterns for uniform presentation of
ICAM-1 along the cell surface and specific apical sorting of RANTES may serve to mediate
the level and directionality of T cell traffic through epithelium (distinct from endothelium) and
provide a basis for how this process is precisely coordinated to route immune cells to the mucosal surface and maintain them there under normal and stimulated conditions.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
| TABLE OF CONTENTS |
|
