MALFORMIN-A1 INHIBITS THE BINDING OF INTERLEUKIN-1-BETA (IL1-BETA) AND SUPPRESSES THE EXPRESSION OF TISSUE FACTOR IN HUMAN ENDOTHELIAL-CELLS AND MONOCYTES

Malformin-A1, a cyclic pentapeptide of microbial origin, antagonized i n a competitive manner the binding of I-125-IL1 beta (interleukin-1 be ta) to human monocytes and cultured human umbilical vein endothelial c ells (HUVEC) with IC50 values (doses which reduce specific binding by 50%) of 250 +/- 80 and 230 +/- 25 nM, respectively (N = 3). IL1 increa sed in a dose-dependent manner the expression of tissue factor, a ubiq uitous membrane-anchored glycoprotein that initiates blood coagulation at the surface of HUVEC and human monocytes. Malformin-A1 strongly in hibited IL1-induced tissue factor expression in HUVEC and monocytes wi th IC50 values of 420 +/- 35 and 105 +/- 25 nM, respectively (N = 3), and reduced IL1-induced expression of intercellular adhesion molecule- 1 (ICAM-1, CD54) on HUVEC (IC50= 125 +/- 18 nM) (N = 4). These observa tions demonstrate that malformin-A1 recognizes and blocks IL1 beta bin ding to its receptor sites on monocytes and endothelial cells and prot ects these cells from IL1-induced procoagulant changes.