Characterization of a neutrophil inhibitor peptide harvested from human bronchial lavage: homology to influenza A nucleoprotein.
Bronchi are exposed to particulate matter, including bacteria, fungi and dusts, that should trigger release of molecules which attract polymorphonuclear neutrophils (PMN). However, normal bronchi are relatively devoid of PMN, suggesting that there exists a mechanism to dampen acute inflammation in the lung. We have previously reported that bronchial lavage from normal humans contains a nonpolar peptide that inhibits PMN chemotaxis and oxidant production. In the present study we devised preparative methods to obtain sufficient quantities of a similar inhibitor molecule for partial amino acid sequencing and allow production of truncated analogues. Amino acid sequencing demonstrated that the peptide includes a 10-amino-acid sequence that is completely homologous to a sequence of amino acids contained in the influenza A nucleoprotein. Synthesized peptides containing this 10-amino-acid sequence inhibited PMN chemotaxis and oxidant production. In addition, PMN lysates actively phosphorylated peptides containing the 10-amino-acid sequence or a partial sequence containing an apparent phosphorylation site. U937 cells were noted to be one source of this inhibitor, as a similarly sized nonpolar inhibitor peptide was purified from U937 culture supernatants. In addition, U937 and monocyte cellular lysates contained proteins recognized by an antiserum directed at the influenza A nucleoprotein. Further characterization of the molecule described in this study or related molecules may lead to significantly new antiinflammatory strategies.
Cooper
J A
JA
Pulmonary Section, Birmingham Veterans Administration Medical Center (VAMC), Alabama, USA.
Culbreth
R R
RR
D000595:Amino Acid Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002630:Chemotactic Factors / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification; D002633:Chemotaxis / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D015151:Immunoblotting; D009980:Influenza A virus / Q000737:chemistry; D015473:Leukemia, Promyelocytic, Acute; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000737:chemistry* / Q000201:enzymology; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000737:chemistry* / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification; D010766:Phosphorylation; D016601:RNA-Binding Proteins; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000378:metabolism; D014758:Viral Core Proteins / Q000737:chemistry* / Q000494:pharmacology
D002630:Chemotactic Factors; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010455:Peptides; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D013481:Superoxides