A Neutrophil-dependent Pathway for the Generation of a Neutral Peptide Mediator Partial Characterization of Components and Control by O~-i-antitrypsin* by Bruce U. Wintroub,$ Edward J. Goetzl,§ and K. Frank Austen

Polymorphonuclear leukocytes have the capacity to supply proteolytic enzymes capable of generating kinin activity from a plasma protein substrate, kininogen, under diverse reaction conditions (1-3). Experiments, initially directed toward the mechanism of neutrophil-dependent kinin generation, have uncovered a different system which is controlled by ec-l-antitrypsin. Incubation of crude neutrophil homogenates with heated human plasma generated a biologically active neutral peptide, distinct from bradykinin, derived from a plasma protein substrate chromatographically separable from kininogen. The neutrophil enzyme responsible for the formation of neutral peptide was a serine-dependent protease sensitive to inhibition by plant-derived trypsin inhibitors and a-l-antitrypsin.