The Effect of Fibrinogen Degradation Products on in Vitro Lymphocyte Function

Fibrinogen Degradation Products (FDP) are increased in the sera of patients with advanced cancer and other immunosuppressive states. We studied the effect of micromolecular FDP on the function of normal human lymphocytes.

FDP were obtained by prolonged digestion of human fibrinogen with plasmin. Plasmin was prepared from plasminogen by activation with Streptokinase in 0.1M tris buffer, pH 8.0 at 37°C. After dialysis and lyophilization, terminal FDP were reconstituted in phosphate buffered saline, sterilized and added in varying concentration to a lymphocyte microculture system, sRBC and EAC rosette assays and a Lexy plate Migration Inhibition Factor assay (MIF).

FDP exhibited dose dependent inhibition of lymphocyte blastogenesis induced by the mitogens Phytohemagglutinin (PHA), Concanavillin A (Con A) and Pokeweed (PWM). FDP incubated with lymphocytes had no effect on MIF production or on T and B lymphocyte Rosette formation. FDP were further separated by gel electrophoresis on G–25 Sephadex column. Three peaks were obtained. Peaks 1 and 2 inhibited mitogenic response and Peak 3 enhanced PHA induced lymphocyte blastogenesis. Peaks obtained from the column were further characterized by isoelectric focusing.

Micromolecular FDP appear to play a role in the non-specific modulation of lymphocyte functions that depend on cell replication. Their role should be further investigated in clinical immunosuppressive states.