Regulation of prostaglandin E2 and plasminogen activator by various immunomodulators in human monocytes

Mononuclear phagocyte populations and monocytes are able to produce, among numerous substances, a neutral protease, i.e. plasminogen activator (PA) and prostaglandins. Since it has been shown that prostaglandins (PGs) and particularly PGE2 could exert an inhibitory effect on PA production by macrophages, we have measured the in vitro production of PA and PGE2 by monocytes isolated from healthy donors. These monocytes were cultured either in the absence or the presence of various immunomodulators: lipopolysaccharide from E. coli, concanavalin A and RU 41740 or Biostim a broad spectrum immunostimulating agent isolated from Klebsiella pneumoniae (Cassenne Laboratories, France). The production of PGE2 was proportional to the number of monocytes per incubation, and at a given cell concentration varied greatly from one subject to another. When considering PGE2 productions, the type of the response to the different immunomodulators varied from subject to subject and ranged from stimulation to no effect, or even inhibition. Moreover, a statistically significant, inverse relationship exists between the spontaneous production of PGE2 and the effect of each immunomodulator. For a given subject, all agents always acted in the same way and there was an inverse relationship between the effects of the immunomodulators on plasminogen activator and PGE2 production.