KUNITZ-TYPE TRYPSIN-INHIBITOR PREVENTS LPS-INDUCED INCREASE OF CYTOSOLIC-FREE CA2+ IN HUMAN NEUTROPHILS AND HUVEC CELLS

The protease inhibitor part of inter-alpha trypsin inhibitor is identical to urinary trypsin inhibitor (UTI). Preincubation of neutrophils and HUVEC cells with UTI inhibited increase of cytosolic free Ca2+ induced by LPS. Increase of cytosolic free Ca2+ induced by LPS in the presence of EGTA was also inhibited by UTI. In contrast, UTI did not inhibit increase of cytosolic free Ca2+ in cells stimulated by Ca2+ ionophore with or without EGTA. The effects of nine synthetic peptides of UTI on the concentration of cytosolic free Ca2+ in the neutrophils induced by LPS were examined. Preincubation with a peptide of UTI domain 2, NLPIVRGPCRAFIQL (83-97), was completely inhibited by the increase of cytosolic free Ca2+ in neutrophils. This region is identical to the trypsin inhibitor site of UTI. We propose that a function of UTI other than as a protease inhibitor is in regulation of intracellular Ca2+ and that this is due to its trypsin inhibitor region. (C) 1995 Academic Press, Inc.