Time-dependent inhibition of tuberculin-induced lymphocyte DNA synthesis by a serine protease inhibitor.
Diisopropylfluorophosphate (DFP), a group-specific irreversible inhibitor of serine proteases, has been shown to exert time-dependent inhibition of DNA synthesis of lymphocytes stimulated by three different B lymphocyte mitogens: purified protein derivative of tuberculin (PPD), endotoxin protein (EP), and lipopolysaccharide (LPS). The time-dependent inhibition profile found in B lymphocytes is absent in concanavalin A (Con A)-stimulated T lymphocytes. Structural analogs of DFP, which have lost the phosphorylating ability, are not inhibitory. Inhibition of DNA synthesis by DFP is reversible in the first 8 hr of mitogenic stimulation. Maximal and irreversible inhibition by DFP occurs around the 16th hour of stimulation. These data support the postulate that a mitogenesis-linked protease, or proteases, in B lymphocytes is absent in the resting cells but is made available several hours before the initiation of DNA synthesis in the late G1 phase of the cell cycle.
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis*; D005260:Female; D007531:Isoflurophate / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D011480:Protease Inhibitors / Q000494:pharmacology*; D013997:Time Factors; D014373:Tuberculin / Q000276:immunology*
D011480:Protease Inhibitors; D014373:Tuberculin; D003208:Concanavalin A; D007531:Isoflurophate; D004247:DNA