Mononuclear phagocytes can be activated to develop enhanced expression of a wide range of macromolecules and mediators. Amongst these are several procoagulants, most notably thromboplastin. A variety of stimuli (particles, ligands for cell surface receptors, and some pharmacological agents) enhance procoagulant expression. We indicate that such enhancement may contribute to intra-and extravascular coagulation in several types of infections. We also point to the paucity of knowledge on the biosynthesis and intracellular transport of these procoagulants and speculate on the nature of the mechanisms involved.

No abstract

Peritoneal macrophages from mice infected with Trypanosoma brucei brucei expressed a greatly elevated procoagulant activity (PCA) which could be reversed to normal levels after trypanocidal therapy. Comparison with infection caused by the non-pathogenic T. musculi suggested that the level of PCA related to parasite pathogenicity. Unstimulated macrophages, which generate only slight PCA upon stimulation with zymosan, become hyperresponsive to this stimulus during the course of infection. Hyperresponsiveness is not a generalized feature of these cells during infection, as they become progressively hyporesponsive to the same stimulus in terms of lysosomal enzyme secretion. We were unable to demonstrate a direct role of the trypanosomes in macrophage activation; however, artificial removal of the glycoprotein coat rendered the parasites highly stimulatory for macrophages even in the absence of opsonins. These results suggest that the parasites may activate macrophages indirectly, and that the resulting elevated PCA may play a role in the abnormal blood coagulation known to occur in this disease.

We have previously shown that peritoneal macrophages from Trypanosoma brucei infected mice, but not from uninfected mice, expressed high levels of procoagulant activity that could not be produced in vitro by incubation of unstimulated macrophages with bloodstream forms of trypanosomes. In the present study we demonstrate that trypanosome-induced macrophage activation can be achieved in vitro by providing either sensitized (day 7 of infection) lymphocytes and trypanosomes or the supernatant fluid from this interaction. The ability of lymphocytes to secrete macrophage-activating lymphokines is enhanced up to day 12 of infection but was absent in the later stages. Although enhancement of the procoagulant activity occurred in infected nude mice, it seems that macrophage function in African trypanosomiasis, as regards the expression of procoagulant activity, is regulated by T-lymphocytes.