Stimulation of integrin-mediated adhesion of T lymphocytes and monocytes: two mechanisms with divergent biological consequences.

Abstract

SummaryWe 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 antiq~l integrin monodonal antibody 8A2. The second is by treating the ceUs 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.

The Affinity of Integrin α4β1 Governs Lymphocyte Migration

“…Thus, the high-affinity ␣ 4 ␤ 1 on Jurkat cells do not appear to play a major role in regulating static cell adhesion. This finding is not unique to ␣ 4 ␤ 1 , as integrin ␣ 5 ␤ 1 activation also plays only a minor role in static cell adhesion (21). Furthermore, wild-type and ␣ 4 ␤ 1 activation-defective Jurkat cells showed similar tethering/rolling and adhesion strengthening on VCAM-1 under flowing conditions.…”

Differential adhesion pattern of B cell chronic lymphocytic leukemia cells

“…This interpretation is supported by previous findings that integrin-mediated adhesion is mediated by a rapid increase of the affinity of these molecules towards their respective ligands. 14,47 However, the fact that the anti-CD19-induced aggregation could be blocked by cycloheximide demonstrated that initiation of homotypic adhesion also depended on protein synthesis. The activity of integrin molecules is influenced by a large number of regulatory proteins (reviewed in Ref.…”

α4β1 Integrin/VCAM-1 Interaction Activates αLβ2 Integrin-Mediated Adhesion to ICAM-1 in Human T Cells

“…Avidity changes, which include integrin clustering, association with the cell cytoskeleton, and activation-dependent cell spreading, up-regulate integrin ligand binding without affecting affinity. Phorbol ester treatment of T cells triggers ␤ 1 and ␤ 2 integrin-mediated adhesion and cell spreading in the absence of changes in integrin affinity (14,15). Similarly, cross-linking the TCR complex induces cell flattening, association of integrins with cytoskeletal proteins, and adhesion to VCAM-1 and ICAM-1 without altering integrin affinity (15)(16)(17).…”