Key result
Inhibitor cocktail reduces LPS-induced TF activity ~77%, dependent on protease, thromboxane A2, and PAF antagonists.
In human whole blood ex vivo, inhibition of LPS-induced monocyte tissue factor activity and TNF-alpha release depends on the combined blockade of serine proteases, thromboxane A2, and PAF receptors.
Answers are grounded in this paper and cite their sources.
May attenuate LPS-driven inflammation via combined blockade in ex vivo blood; leaves open translation to clinical sepsis therapy.
Expression of tissue factor (TF) by activated monocytes may initiate thrombotic episodes associated with diseases, such as thrombosis and atherosclerosis. In this study, steps in the regulatory pathways of lipopolysaccharide (LPS)-induced monocyte TF activity and released TNF-alpha in human whole blood were probed for using an array of inhibitors, comprising specific inhibitors of cytosolic phospholipase A(2) (PLA(2)) (AACOCF(3)), secretory PLA(2) (SB-203347), protein kinase (PK) (staurosporine), PKC (GF-109203; BIM), and serine protease (Pefabloc SC), antagonists of thromboxane prostanoid (TP) receptor (R) (SQ-29548), platelet activating factor (PAF) R (BN-52021), leukotriene B(4) R (SC-41930), serotonin R (cyproheptadine), fibronectin/fibrinogen R (RGDS), and finally, creatine phosphate/creatine phosphokinase (CP/CPK) which removes ADP. Whereas when added alone neither of these agents significantly inhibited LPS-induced TF or TNF-alpha, when presented as a reference cocktail comprising all the agents, TF activity and TNF-alpha were reduced by 77% and 49%, respectively. By subsequently testing a series of incomplete inhibitory cocktails equal to the reference except for deleted single agents or combinations of two or three active agents, the inhibitory effect of the reference cocktail could be shown to depend on the presence of the protease inhibitor and the thromboxane A(2) and PAF antagonists.
No takes yet. Share an insight, caveat, or question.
Eilertsen et al. (2002) studied LPS-induced monocyte tissue factor activity in human whole blood. Reference cocktail of inhibitors vs. Single agents or incomplete inhibitory cocktails was evaluated on LPS-induced monocyte tissue factor (TF) activity and released TNF-alpha. A reference cocktail of inhibitors reduced LPS-induced tissue factor activity and TNF-alpha by 77% and 49%, respectively, an effect dependent on protease, thromboxane A2, and PAF antagonists.
Synapse has enriched 10 related papers. Consider them for comparative context: