Elevated thrombomodulin plasma levels as a result of endothelial involvement in plasmodium falciparum malaria.
We used thrombomodulin (TM) to assess the participation of the vascular endothelium in human Plasmodium falciparum (P.F.) malaria. Before therapy TM plasma levels were elevated in P.F. malaria and fell to normal values during therapy. Parasitemia, TNF alpha, elastase and TAT levels correlated directly with TM. Elevated TM levels can not be explained by increased synthesis, since incubating HUVEC with pretherapy serum of patients with P.F. malaria, but not reconvalescence serum, suppressed TM transcription. This was partially prevented by adding a TNF alpha neutralizing antibody to patient serum before incubation with HUVEC. However, TNF alpha does not release TM from cultured HUVEC in vitro. Coincubation of HUVEC with pretherapy serum together with neutrophils resulted in endothelial cell destruction, which could be partly prevented 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.
Hemmer
C J
CJ
Department of Medicine, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany.
Bierhaus
A
A
von Riedesel
J
J
Gabat
S
S
Liliensiek
B
B
Pitronik
P
P
Lin
J
J
Grauer
A
A
Amiral
J
J
Ziegler
R
R
D000962:Antimalarials / Q000627:therapeutic use; D000990:Antithrombin III / Q000032:analysis; D002478:Cells, Cultured; D003289:Convalescence; D004730:Endothelium, Vascular / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology; D005786:Gene Expression Regulation; D006801:Humans; D019272:Leukocyte Elastase; D016778:Malaria, Falciparum / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D009504:Neutrophils / Q000502:physiology; D010196:Pancreatic Elastase / Q000097:blood; D018512:Parasitemia / Q000378:metabolism / Q000473:pathology; D010447:Peptide Hydrolases / Q000032:analysis; D011446:Prospective Studies; D018180:Thrombomodulin / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000962:Antimalarials; D018180:Thrombomodulin; D014409:Tumor Necrosis Factor-alpha; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase