ELEVATED THROMBOMODULIN PLASMA-LEVELS AS A RESULT OF ENDOTHELIAL INVOLVEMENT IN PLASMODIUM-FALCIPARUM MALARIA

We used thrombomodulin (TM) to assess the participation of the vascula r endothelium in human Plasmodium falciparum (P. F.) malaria. Before t herapy TM plasma levels were elevated in P. F. malaria and fell to nor mal values during therapy. Parasitemia, TNF alpha, elastase and TAT le vels correlated directly with TM. Elevated TM levels can not be explai ned by increased synthesis, since incubating HUVEC with pretherapy ser um of patients with P. F. malaria, but not reconvalescence serum, supp ressed TM transcription. This was partially prevented by adding a TNF alpha neutralizing antibody to patient serum before incubation with HU VEC. However, TNF alpha does not release TM from cultured HUVEC in vit ro. Coincubation of HUVEC with pretherapy serum together with neutroph ils resulted in endothelial cell destruction, which could be partly pr evented by a TNF alpha neutralizing antibody. Hence the increase of TM during P. F. malaria might reflect the concerted action of cytokines and neutrophils on HUVEC.