Am. J. Respir. Cell Mol. Biol., Vol 15, No. 2, 08 1996, 207-215.
Characterization of a neutrophil inhibitor peptide harvested from human bronchial lavage: homology to influenza A nucleoprotein
JA Cooper Jr and RR Culbreth
Pulmonary Section, Birmingham Veterans Administration Medical Center (VAMC), Alabama, USA.
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.
