Neutrophil Migration across Cultured Intestinal Epithelial Monolayers Is Modulated by Epithelial Exposure to IFN-γ in a Highly Polarized Fashion

• Published in: The Journal of cell biology 1993-02, Vol.120 (3), p.785-798
• Main Authors: Colgan, Sean P., Parkos, Charles A., Delp, Charlene, Arnaout, M. Amin, Madara, James L.
• Format: Article
• Language: English
• Subjects: Antibodies; Antigens, CD - physiology; Biological and medical sciences; CD11 Antigens; CD18 Antigens; Cell Adhesion; Cell Adhesion Molecules - analysis; Cell Adhesion Molecules - physiology; Cell Communication - drug effects; Cell Line; Cell lines; Cell physiology; Cells, Cultured; Chemotaxis, Leukocyte - drug effects; Cytokines; Endothelial cells; Endothelium, Vascular - physiology; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Epithelium - drug effects; Epithelium - physiology; Fundamental and applied biological sciences. Psychology; Human migration; Humans; Intercellular Adhesion Molecule-1; Interferon-gamma - pharmacology; Intestines - cytology; Intestines - drug effects; Intestines - physiology; Molecular and cellular biology; Neutrophils; Neutrophils - cytology; Neutrophils - drug effects; Neutrophils - physiology; Recombinant Proteins; Responses to growth factors, tumor promotors, other factors; Tight junctions; Transmigration; Umbilical Veins; Up regulation
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.120.3.785

Neutrophil, or polymorphonuclear leukocyte (PMN), migration across intestinal epithelial barriers, such as occurs in many disease states, appears to result in modifications of epithelial barrier and ion transport functions (Nash, S., J. Stafford, and J. L. Madara. 1987. J. Clin. Invest. 80:1104-1113; Madara, J. L., C. A. Parkos, S. P. Colgan, R. J. MacLeod, S. Nash, J. B. Matthews, C. Delp, and W. I. Lencer. 1992. J. Clin. Invest. 89:1938-1944). Here we investigate the effects of epithelial exposure to IFN-γ on PMN migration across cultured monolayers of the human intestinal epithelial cell line T84. Transepithelial migration of PMN was initially assessed in the apical-to-basolateral direction, since previous studies indicate general qualitative similarities between PMN migration in the apical-to-basolateral and in the basolateral-to-apical directions. In the apical-to-basolateral direction, epithelial exposure to IFN-γ markedly upregulated transepithelial migration of PMN in a dose- and time-dependent fashion as measured by both electrical and myeloperoxidase assays. This IFN-γ-elicited effect on transmigration was specifically due to a IFN-γ effect on epithelial cells and was not secondary to IFN-γ effects on epithelial tight junction permeability. Moreover, this IFN-γ effect was dependent on epithelial protein synthesis, and involved a pathway in which CD11b/18, but not ICAM-1 or CD11a/18, appeared to play a crucial role in PMN-epithelial adhesion. IFN-γ also substantially modified PMN transepithelial migration in the natural, basolateral-to-apical direction. The IFN-γ effect on naturally directed transmigration was also specifically due to an IFN-γ effect on epithelial cells, showed comparable time and dose dependency to that of oppositely directed migration, was CD11b/18 dependent, and required epithelial protein synthesis. Additionally, however, important qualitative differences existed in how IFN-γ affected transmigration in the two directions. In contrast to apical-to-basolateral directed migration, IFN-γ markedly downregulated transepithelial migration of PMN in the natural direction. This downregulation of PMN migration in the natural direction, however, was not due to failure of PMN to move across filters and into monolayers. Indeed, IFN-γ exposure to epithelia increased the number of PMN which had moved into the basolateral space of the epithelium in naturally directed transmigration. These results represent the first detailed report of influen