LFA-1 integrin redistribution during T-cell hybridoma invasion of hepatocyte cultures and manganese-induced adhesion to ICAM-1
| Autor: | A. M. L. Meijne, G. La Riviere, M. H. E. Driessens, Ed Roos, D. Casey, Constance A. Feltkamp |
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| Rok vydání: | 1994 |
| Předmět: |
T-Lymphocytes
T cell Integrin Intercellular Adhesion Molecule-1 chemical and pharmacologic phenomena Biology Lymphoma T-Cell Cell Fusion Cell Adhesion medicine Animals Cytotoxic T cell Neoplasm Invasiveness Lymphocyte function-associated antigen 1 Microscopy Immunoelectron Cell adhesion Cells Cultured Manganese Hybridomas Cell Biology Lymphocyte Function-Associated Antigen-1 Neoplasm Proteins Rats Cell biology medicine.anatomical_structure Liver Biochemistry Hepatocyte biology.protein Filopodia T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of Cell Science. 107:2557-2566 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.107.9.2557 |
| Popis: | We have reported previously that the integrin LFA-1 is essential for metastasis of T-cell hybridomas to the liver. We show here that hepatocytes isolated from normal non-inflamed rat liver express intercellular adhesion molecule-1 (ICAM-1) at the dorsal surface and more prominently at the lateral and substratum-adherent surfaces. Anti-rat ICAM-1 mAb inhibited adhesion of TAM8C4 T-cell hybridoma cells to hepatocytes. Invasion between hepatocytes was not affected, but this is probably due to lack of penetration of the mAb between the hepatocytes. In all hepatocyte-adherent TAM8C4 cells, LFA-1 was concentrated at the adhesion site. Redistribution of ICAM-1 to the interacting hepatocyte membrane was also seen, but only for part of the adherent TAM8C4 cells. LFA-1 was highly concentrated on pseudopods of invading TAM8C4 cells inserted between hepatocytes, and on the upper surface of invaded TAM8C4 cells located under the hepatocytes. ICAM-1 was concentrated in the hepatocyte membrane overlying TAM8C4 cells located underneath the monolayer. These results suggests that ICAM-1 is of major importance for liver invasion by these lymphoma cells. For optimal adhesion to ICAM-1, LFA-1 on T-cell hybridomas requires activation, which apparently occurs upon contact with cell layers that are invaded (G. La Riviere et al., J. Cell Sci. 107, 551–559, 1994). LFA-1 can be activated artificially by Mn2+. To study LFA-1 redistribution upon ICAM-1 interaction with higher resolution, we performed immuno-EM on cells before and after Mn(2+)-induced adhesion and spreading on immobilized ICAM-1. By immune fluorescence, LFA-1 was observed to redistribute to the ICAM-1-adherent surface, and to be concentrated in lamellipodia of spreading TAM8C4 cells. By immuno-EM, LFA-1 was localized in microclusters of approximately 10 gold particles. This was seen in cells fixed in suspension, and the size of these clusters did not change upon adhesion to ICAM-1. LFA-1 was present at high density in thin filopodia, but again in microclusters of similar size. Comparable results were obtained with a cytotoxic T-cell clone. We conclude that Mn(2+)-induced activation of LFA-1 is not associated with the formation or enlargement of LFA-1 clusters. |
| Databáze: | OpenAIRE |
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