AJP - Cell Physiology, Vol 271, Issue 1 C312-C320, Copyright © 1996 by American Physiological Society

ARTICLES

Intestinal epithelial cytoskeleton selectively constrains lumen-to-tissue migration of neutrophils

P. Hofman, L. D'Andrea, D. Carnes, S. P. Colgan and J. L. Madara
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

Migration of neutrophils (polymorphonuclear leukocytes; 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 preloading monolayers with the F-actin stabilizing agent phallacidin. Although phallacidin preloading 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). 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (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 phallacidin 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 that biases for retention of PMN in the luminal space.

This article has been cited by other articles:

				F. Betis, P. Brest, V. Hofman, J. Guignot, I. Kansau, B. Rossi, A. Servin, and P. Hofman Afa/Dr Diffusely Adhering Escherichia coli Infection in T84 Cell Monolayers Induces Increased Neutrophil Transepithelial Migration, Which in Turn Promotes Cytokine-Dependent Upregulation of Decay-Accelerating Factor (CD55), the Receptor for Afa/Dr Adhesins Infect. Immun., April 1, 2003; 71(4): 1774 - 1783. [Abstract] [Full Text]

				F. Betis, P. Brest, V. Hofman, J. Guignot, M.-F. Bernet-Camard, B. Rossi, A. Servin, and P. Hofman The Afa/Dr Adhesins of Diffusely Adhering Escherichia coli Stimulate Interleukin-8 Secretion, Activate Mitogen-Activated Protein Kinases, and Promote Polymorphonuclear Transepithelial Migration in T84 Polarized Epithelial Cells Infect. Immun., March 1, 2003; 71(3): 1068 - 1074. [Abstract] [Full Text] [PDF]

				P. Brest, B. Mograbi, V. Hofman, A. Loubat, B. Rossi, P. Auberger, and P. Hofman Rho GTPase Is Activated by Cytotoxic Necrotizing Factor 1 in Peripheral Blood T Lymphocytes: Potential Cytotoxicity for Intestinal Epithelial Cells Infect. Immun., March 1, 2003; 71(3): 1161 - 1169. [Abstract] [Full Text] [PDF]

				G. Le'Negrate, E. Selva, P. Auberger, B. Rossi, and P. Hofman Sustained Polymorphonuclear Leukocyte Transmigration Induces Apoptosis in T84 Intestinal Epithelial Cells J. Cell Biol., September 18, 2000; 150(6): 1479 - 1488. [Abstract] [Full Text] [PDF]

				L. Pizurki, M. A. Morris, M. Chanson, M. Solomon, A. Pavirani, I. Bouchardy, and S. Suter Cystic Fibrosis Transmembrane Conductance Regulator Does Not Affect Neutrophil Migration across Cystic Fibrosis Airway Epithelial Monolayers Am. J. Pathol., April 1, 2000; 156(4): 1407 - 1416. [Abstract] [Full Text] [PDF]

				N.-O. Ku, X. Zhou, D. M. Toivola, and M. B. Omary The cytoskeleton of digestive epithelia in health and disease Am J Physiol Gastrointest Liver Physiol, December 1, 1999; 277(6): G1108 - G1137. [Abstract] [Full Text] [PDF]

				D. Merlin, L. Jiang, G. R. Strohmeier, A. Nusrat, S. L. Alper, W. I. Lencer, and J. L. Madara Distinct Ca2+- and cAMP-dependent anion conductances in the apical membrane of polarized T84 cells Am J Physiol Cell Physiol, August 1, 1998; 275(2): C484 - C495. [Abstract] [Full Text] [PDF]

				C. A. Parkos I. Neutrophil adhesive interactions with intestinal epithelium Am J Physiol Gastrointest Liver Physiol, October 1, 1997; 273(4): G763 - G768. [Abstract] [Full Text] [PDF]

				D. W. Lawrence, K. M. Comerford, and S. P. Colgan Role of VASP in reestablishment of epithelial tight junction assembly after Ca2+ switch Am J Physiol Cell Physiol, June 1, 2002; 282(6): C1235 - C1245. [Abstract] [Full Text] [PDF]