Release of a lymphokine-like plasminogen activator by stimulated B lymphocytes

This report extends to the guinea pig the discovery of a lymphocyte plasminogen activator (LPA) previously described in the mouse. In the guinea pig, we have identified enzymatic activity similar to that in the mouse, but which has two distinct components: first, as in the mouse, a membrane-bound molecule present even in the quiescent lymphocyte (mLPA), and second, a previously unreported soluble molecule appearing in the culture medium after appropriate cell stimulation (sLPA). This sLPA, like most known lymphokines, was released by in vitro recall of sensitized lymphocytes by the antigen and by direct contact with a mitogen. There was a parallel evolution in the culture for sLPA and for some other well-known lymphokines (LT, LIF), and their detection thresholds were of the same order. A possible activation of plasminogen (Pg) by macrophages contaminating the lymphocyte cultures was carefully rule out. sLPA was produced by lymph node lymphocytes as well as by blood lymphocytes, but not by spleen cells, thymocytes, or peritoneal lymphocytes. A study of the kinetics of the release of sLPA, together with that of metabolic modifiers, suggested that an intracellular synthesis precedes the secretion of the molecule. Data obtained from the use of B- and T-enriched subpopulations or B- or T-dependent antigens and mitogens point to the B lymphocytes as the major, if not exclusive, source of sLPA. The choice of synthetic chromogenic substrates S 2251, S 2444, and S 2288 in some experiments led us to confirm most of the above properties of sLPA with still greater precision and reliability.