Modulation of rat lymphocyte transformation by plasma fibronectin

Purified rat plasma fibronectin (Fn) was studied for its ability to influence nonspecific lymphocyte transformation to various mitogens. Fn added to lymph node cells (LNC) stimulated with phytohemagglutinin (PHA), concanavalin A (Con A), or bacterial lipopolysaccharide (LPS) resulted in a noncytotoxic dose-dependent inhibition of the blastogenic response. Effective inhibition (greater than 50%) of LNC responses to PHA and LPS occurred with concentrations of Fn that ranged from 10-50 micrograms/culture. The proliferative response to Con A was less affected by the presence of Fn: 50% inhibition was observed only with the highest concentration of Fn studied. Fn at low concentrations was more effective than Fn-depleted plasma in inhibiting lymphocyte responses to PHA. Optimal expression of the regulatory activity of Fn occurs during and following the peak proliferative period for both PHA and LPS responses. In order to evoke maximum inhibition it is necessary for Fn to be present within 12 hours following stimulation of LNC with mitogen. Inhibition does not appear to be the result of Fn-mitogen complexes which reduce the amount of mitogen available for stimulation, since increasing concentrations of either PHA or LPS did not significantly reduce the inhibitory effect. Furthermore, inhibition was not influenced by the concentration of fetal calf serum present in the culture medium. Thus, Fn may function as an important nonspecific immunoregulatory factor at inflammatory sites and in areas of tissue repair.