A human neutrophil lysosomal
protease interacts at physiologic pH with a 62,000--67,000-mol wt
plasma protein substrate to generate a vasoactive, smooth muscle-contracting "neutral"
peptide. The
peptide product of this system, previously designated the "neutral"
peptide-generating pathway, was generated from purified components and purified by Bio-Gel P2 gel filtration and reverse-phase high performance liquid chromatography with a 50--60% yield of starting activity. The purified
peptide had an
amino acid composition of Asx,
Pro, Val,
Ile, Tyr,
Phe, His, Arg, a composition identical to that of
angiotensin II. The
peptide and synthetic
angiotensin II each filtered at 48--52% bed volume on Bio-Gel P2, had an isoelectric point of Ph 7.8--8.1 at 4 degrees C, migrated 3 cm toward the cathode during pH 6.4 low-voltage paper electrophoresis, and had a retention time of 44.8 min during reverse-phase high-performance liquid chromatography. In addition, the functional activity of the
peptide at each purification step correlated with
angiotensin II content determined by specific radioimmunoassay. The amino acid sequence of 25 nmol of the
peptide was Asp-
Arg-Val-Try-Ile-
His-Pro-Phe, the same covalent structure as that of
angiotensin II. Therefore, under physiologic conditions, in the absence of
renin or
angiotensin converting enzyme, a human neutrophil neutral
protease cleaves a
plasma protein to yield
angiotensin II. This pathway provides a mechanism through which the neutrophil may alter local blood flow during
inflammation by generation of a potent vasoactive
peptide.