Neutrophil-activating intercrine secreted by porcine platelets is active without proteolytic processing.
A new member of the cytokine intercrine alpha-subfamily, porcine neutrophil-activating peptide 2 (pNAP-2), was isolated to homogeneity. Amino acid sequencing analysis showed two species of pNAP-2, a long form (pNAP-2-L) and a short form (pNAP-2-S). pNAP-2-L had seven more amino acids at the NH2-terminus than pNAP-2-S. The remaining amino acid sequences of the two molecules were identical. pNAP-2-S shared 65% homology with human neutrophil-activating peptide 2 (hNAP-2) including four cysteines in identical positions. Moreover, the NH2-terminal sequence Glu-Leu-Arg (E-L-R) was conserved in both molecules. Both pNAP-2-L and pNAP-2-S induced mobilization of cytosolic calcium in neutrophils and caused release of granulocyte elastase in a dose-dependent manner, although pNAP-2-L was less active. A desensitization study suggested that both hNAP-2 and pNAP-2-S may act on the same receptor. Whereas human platelets release inactive precursors that can be converted to hNAP-2 by cathepsin G from activated neutrophils, porcine platelets, upon stimulation with thrombin, appear to secrete active forms of pNAP-2. The activated neutrophils are not involved in the generation of pNAP-2.
Yan
Z
Z
Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Holt
J C
JC
Stewart
G J
GJ
Niewiarowski
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002118:Calcium / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D017124:Conserved Sequence; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D066298:In Vitro Techniques; D019272:Leukocyte Elastase; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010196:Pancreatic Elastase / Q000378:metabolism; D010449:Peptide Mapping; D010455:Peptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D013552:Swine; D001620:beta-Thromboglobulin
C061615:PPBP protein, human; D010455:Peptides; D001620:beta-Thromboglobulin; C009862:connective tissue-activating peptide; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D002118:Calcium