A biologically active neutral peptide mediator is cleaved from a plasma protein substrate by an α-1-antitrypsin-inhibitable serine protease apparently residing on the membrane of the human neutrophil. The peptide mediator has an approximate mol wt of 1,000, and is distinguished from the kinin peptides by a neutral isoelectric point, susceptibility to inactivation by trypsin as well as chymotrypsin and activity on the isolated, atropinized, and antihistamine-treated guinea pig ileum with relatively little action on the estrous rat uterus. The neutrophil protease is fully inhibitable by DFP, trypsin inhibitors from lima or soy bean, and α-1-antitrypsin and is associated with the high mol wt fragments of the neutrophil and not the nuclear, lysosomal, or cytoplasmic subcellular fraction. The substrate has an approximate mol wt of 90,000 and is chromatographically separable from kininogen. The exquisite sensitivity of the neutrophil protease to α-1-antitrypsin was established both by inhibition with highly purified α-1-antitrypsin and by the inability of the protease to generate detectable neutral peptide in a homozygous (ZZ) α-1-antitrypsin-deficient patient without heat inactivation of the residual inhibitor. On the other hand, plasma from a (null) α-1-antitrypsin-deficient patient supported neutral peptide generation and revealed an additional factor which inactivated neutral peptide.
Article|
September 01 1974
A NEUTROPHIL-DEPENDENT PATHWAY FOR THE GENERATION OF A NEUTRAL PEPTIDE MEDIATOR : PARTIAL CHARACTERIZATION OF COMPONENTS AND CONTROL BY α-1-ANTITRYPSIN
Bruce U. Wintroub,
Bruce U. Wintroub
From the Harvard Medical School, Robert B. Brigham Hospital, Boston, Massachusetts 02120
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Edward J. Goetzl,
Edward J. Goetzl
From the Harvard Medical School, Robert B. Brigham Hospital, Boston, Massachusetts 02120
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K. Frank Austen
K. Frank Austen
From the Harvard Medical School, Robert B. Brigham Hospital, Boston, Massachusetts 02120
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Bruce U. Wintroub
From the Harvard Medical School, Robert B. Brigham Hospital, Boston, Massachusetts 02120
Edward J. Goetzl
From the Harvard Medical School, Robert B. Brigham Hospital, Boston, Massachusetts 02120
K. Frank Austen
From the Harvard Medical School, Robert B. Brigham Hospital, Boston, Massachusetts 02120
Received:
May 20 1974
Online ISSN: 1540-9538
Print ISSN: 0022-1007
Copyright © 1974 by The Rockefeller University Press
1974
J Exp Med (1974) 140 (3): 812–824.
Article history
Received:
May 20 1974
Citation
Bruce U. Wintroub, Edward J. Goetzl, K. Frank Austen; A NEUTROPHIL-DEPENDENT PATHWAY FOR THE GENERATION OF A NEUTRAL PEPTIDE MEDIATOR : PARTIAL CHARACTERIZATION OF COMPONENTS AND CONTROL BY α-1-ANTITRYPSIN . J Exp Med 1 September 1974; 140 (3): 812–824. doi: https://doi.org/10.1084/jem.140.3.812
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