Hydrolysis of kininogens by degranulated human neutrophils and analysis ofbradykinin as chemotactic factor for cells isolated from peripheral blood

Human neutrophils play a pivotal role in acute inflammation including the r egulation of vascular permeability, We have examined the capacity of neutro phil enzymes to hydrolyse human kininogens in vitro and have also explored the potentiality of bradykinin to induce chemotactic migration on neutrophi ls isolated from peripheral blood, Isolated neutrophils were stimulated wit h either f-Met-Leu-Phe, thrombin or silica particles coated with human IgG, Neutrophil enzymes obtained by degranulation produced, after 45 min of inc ubation with high and low molecular weight kininogens, the complete transfo rmation of both proteins in polypeptides ranging from 20 to less than 10 kD a in molecular mass, Supernatants obtained from nonstimulated neutrophils d id not modify the molecular size of kininogens. The assay used to test the chemoattractant capacity of synthetic bradykinin on human neutrophils showe d that this peptide has no chemotactic activity on cells isolated from heal thy subjects. Our results show that stimulation of human neutrophils with o psonized silica, thrombin and the chemotactic peptide f-Met-leu-Phe induces release of kininogen-hydrolyzing enzymes from these cells. (C) 1993 Elsevi er Science B.V. All rights reserved.