Generation of the neutrophil-activating peptide NAP-2 from platelet basic protein or connective tissue-activating peptide III through monocyte proteases.
We studied the origin of the neutrophil-activating peptide NAP-2, a presumed 70 amino acid cleavage product of platelet basic protein (PBP) and connective tissue-activating peptide III (CTAP-III). Purified human blood monocytes or lymphocytes were cultured with or without stimuli (LPS or PHA) in the presence or absence of platelet-release supernatant, and the formation of NAP-2 and other neutrophil-activating peptides was monitored. NAP-2 was generated whenever monocytes and platelet release supernatant were present. When a monocyte stimulus was added, NAF/NAP-1 was also formed, and in the presence of LPS a third, less potent neutrophil-stimulating fraction, consisting of NAP-2 variants with 73, 74, and 75 residues, also appeared. Monocytes alone did not yield NAP-2 and no neutrophil-activating peptide was generated by lymphocytes. The monocyte-conditioned medium was found to cleave purified CTAP-III into NAP-2 through proteinases that were highly sensitive to PMSF, moderately sensitive to leupeptin and insensitive to EDTA.
Theodor-Kocher Institute, University of Bern, Switzerland.
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Walz
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Baggiolini
D000595:Amino Acid Sequence; D018925:Chemokines; D006801:Humans; D016209:Interleukin-8; D008969:Molecular Sequence Data; D009000:Monocytes / Q000201:enzymology*; D010452:Peptide Biosynthesis; D010447:Peptide Hydrolases / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D001620:beta-Thromboglobulin
D018925:Chemokines; D016209:Interleukin-8; C061615:PPBP protein, human; D010455:Peptides; D011506:Proteins; D001620:beta-Thromboglobulin; C009862:connective tissue-activating peptide; D010447:Peptide Hydrolases