Stimulation of integrin-mediated adhesion of T lymphocytes and monocytes: two mechanisms with divergent biological consequences.
We show that the adhesion of T lymphoid cells to immobilized fibronectin can be increased by two distinct mechanisms. The first is by increasing the affinity of the fibronectin receptor/ligand interaction using the anti-beta 1 integrin monoclonal antibody 8A2. The second is by treating the cells with phorbol 12-myristate 13-acetate (PMA), which alters events that occur after receptor occupancy (e.g., cell spreading) without affecting receptor affinity. The effects of these two mechanisms on adhesion in the presence of physiological concentrations of soluble fibronectin suggest that they have different biological consequences. Under these conditions, the net effect of increasing the affinity of the fibronectin receptors is to decrease cell adhesion, whereas the increase in adhesion induced by PMA is unaffected. This suggests that the high affinity receptors are not primarily available for cell adhesion under these circumstances, and that they have an alternative function. We further show that high affinity binding of soluble fibronectin can be induced by either differentiation of the monocytic cell line THP-1 or by cross-linking the T cell receptor complexes on the T lymphoid cell line HUT-78. The differentiated monocytic cells express two populations of fibronectin receptors: a minority in a high affinity state, and the majority in a low affinity state. Thus they will both continue to adhere in the presence of physiological concentrations of soluble fibronectin and bind significant amounts of soluble fibronectin at the cell surface.
Faull
R J
RJ
Committee on Vascular Biology, Scripps Research Institute, La Jolla, California 92037.
Kovach
N L
NL
Harlan
J M
JM
Ginsberg
M H
MH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion; D002454:Cell Differentiation; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D017469:Receptors, Fibronectin / Q000378:metabolism; D012995:Solubility; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D017469:Receptors, Fibronectin; D013755:Tetradecanoylphorbol Acetate