Anchorage and lymphocyte function: extracellular matrix substrata control morphogenesis and interleukin production but have minor effects on DNA synthesis.

Abstract

Contact with collagen and fibronectin substrata triggers disruption of aggregates of activated lymphocytes, pseudopodia formation and migration of these lymphocytes onto the substrata. Monoclonal antibodies to the alpha 4 and alpha 5 chains of beta 1-integrins inhibit cell substrate adhesion and aggregate disruption on fibronectin substrata. A rat monoclonal antibody to the beta 1-integrin chain inhibits lymphocyte adhesion to collagen. Two-dimensional (2D) and three-dimensional (3D) collagen substrata have virtually the same capacity to abrogate lymphocyte aggregation. Fibronectin substrata trigger the initial phase(s) of aggregate disruption as effectively as collagen but the later part of the disruption process is relatively incomplete. Serum-coated plastic does not cause aggregate disruption. These results indicate that disruption of lymphocyte aggregates is a specific event induced via cell surface receptors for extracellular matrix (ECM) components. A major difference between lymphocytes on 2D and 3D extracellular matrix substrata seems to be that the cells detach from the former whereas on the latter infiltration dominates over detachment. Collagen and fibronectin substrata are non-mitogenic for lymphocytes but they can modulate lymphocyte activation induced by allogeneic cells and Con A. Thus, 3D collagen substrata augment and prolong such induced DNA synthesis, although they slightly delay entry into the S-phase and decrease IL-2 production. Collagen substrata, particularly in 3D form, also augment the DNA synthesis of preactivated lymphocytes above the magnitude on serum-coated plastic. The nature of the substratum determines IL-1 production. Accordingly, the spontaneous IL-1 production by mononuclear cells is substantially lower on collagen substrata than on plastic surfaces coated with serum or BSA. However, factors which induce IL-1 production (e.g. Con A or LPS) are more effective on collagen than on serum-coated plastic. Abrogation of cell aggregation, induction of morphogenesis and motile behaviour as well as control of IL-1 synthesis thus constitute major effects of ECM substrata on cells of the immune system. An additional but relatively minor influence of ECM substrata on these cells, as suggested by the present results, is exerted via modulation of DNA synthesis.