The intersubject variability of tissue factor mRNA production in human monocytes--relation with the toll-like receptor 4.
OBJECTIVE
Tissue factor (TF) is known as the primary initiator of blood coagulation. Previous studies have suggested a considerable variation in the monocytic lipopolysaccharide (LPS) stimulated TF antigen levels and procoagulant activities between different individuals. Our aim with the present study was to investigate the replicability of LPS induced TF mRNA production in a series of standardised experiments with the purpose to identify putative factors influencing the TF high and low response.


RESULTS
A constant and reproducible production of LPS induced TF mRNA was identified in five high responders and three low responders (out of 42 individuals) and followed-up in three subsequent experiments performed over 2 years. The LPS induced TF mRNA production correlated with the corresponding expressions of interleukin-8, tumor necrosis factor-alfa and interleukin-1 beta, indicating a common pathway with the TF high and low response. A strong and significant correlation between the LPS induced TF and toll-like receptor 4 mRNA expressions was subsequently identified and replicated.


CONCLUSIONS
We demonstrated a high and low responder phenomenon of LPS induced TF mRNA in human monocytes. The production of toll-like receptor 4 mRNA was significantly enhanced in TF high responders.
Mälarstig
Anders
A
Department of Medical Sciences, Clinical Chemistry, Uppsala University, S-751 85 Uppsala, Sweden.
Siegbahn
Agneta
A
D005500:Follow-Up Studies; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D013925:Thromboplastin / Q000096:biosynthesis*; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053583:Interleukin-1beta; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin