Neutrophil migration across a cultured intestinal epithelium. Dependence on a CD11b/CD18-mediated event and enhanced efficiency in physiological direction.
- 1 November 1991
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 88 (5), 1605-1612
- https://doi.org/10.1172/jci115473
Abstract
Neutrophils (PMN) migrate across intestinal epithelia in many disease states. Although such migration serves as a histological index of disease activity, little is known concerning the molecular events underlying PMN-intestinal epithelial interactions. We have studied chemotactic peptide-driven movement of PMN across cultured monolayers of the human intestinal epithelial cell line T84. Using a transmigration microassay, we show that both the decreased transepithelial resistance (76 +/- 3%) and transmigration (4 +/- 0.6 x 10(5) PMN.cm-2, when PMN applied at 6 x 10(6).cm-2) are largely prevented by MAbs which recognize either subunit of the PMN surface heterodimeric adhesion glycoprotein, CD11b/CD18. In contrast, such PMN-epithelial interactions are unaffected by MAbs recognizing either of the remaining two alpha subunits CD11a or CD11c. PMN from a leukocyte adherence deficiency patient also failed to migrate across epithelial monolayers thus confirming a requirement for CD11/18 integrins. By modifying our microassay, we were able to assess PMN transmigration across T84 monolayers in the physiological direction (which, for technical reasons, has not been studied in epithelia): transmigration was again largely attenuated by MAb to CD18 or CD11b (86 +/- 2% and 73 +/- 3% inhibition, respectively) but was unaffected by MAb to CD11a, CD11c. For standard conditions of PMN density, PMN transmigration in the physiological direction was 5-20 times more efficient than in the routinely studied opposite direction.Keywords
This publication has 39 references indexed in Scilit:
- ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18).The Journal of cell biology, 1990
- Constitutive and stimulus-induced phosphorylation of CD11/CD18 leukocyte adhesion molecules.The Journal of cell biology, 1989
- Cytokine-induced respiratory burst of human neutrophils: dependence on extracellular matrix proteins and CD11/CD18 integrins.The Journal of cell biology, 1989
- Recognition of an endothelial determinant for CD 18-dependent human neutrophil adherence and transendothelial migration.JCI Insight, 1988
- Clostridium difficile toxin A perturbs cytoskeletal structure and tight junction permeability of cultured human intestinal epithelial monolayers.JCI Insight, 1988
- Relative contribution of the leukocyte molecules MO1, LFA‐1, and p150,95 (LeuM5) in adhesion of granulocytes and monocytes to vascular endothelium is tissue‐ and stimulus‐specificJournal of Cellular Physiology, 1988
- Neutrophil activation on biological surfaces. Massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes.JCI Insight, 1987
- Effects of polymorphonuclear leukocyte transmigration on the barrier function of cultured intestinal epithelial monolayers.JCI Insight, 1987
- Deficiency of a Granulocyte-Membrane Glycoprotein (gp150) in a Boy with Recurrent Bacterial InfectionsNew England Journal of Medicine, 1982
- A monoclonal antibody to human acute lymphoblastic leukaemia antigenNature, 1980