Am. J. Respir. Crit. Care Med.,
Volume 163, Number 5, April 2001, 1198-1205
Attenuation of Interleukin 8-induced Nasal
Inflammation by an Inhibitor Peptide
J. ALLEN D.
COOPER Jr.,
A. LYNN
RIDGEWAY,
JOHN
PEARSON,
and
RACHEL R.
CULBRETH
Pulmonary Sections, Birmingham Veterans Affairs Medical Center, and University of Alabama at Birmingham, Birmingham, Alabama
Polymorphonuclear neutrophils (PMNs) infiltrate tissue in response
to chemoattractants, including interleukin 8 (IL-8). Infiltrating PMNs clear microorganisms but also cause tissue damage. We previously reported the presence in human bronchial lavage of a peptide that inhibits PMN functions. The current project assessed (1)
effects of a synthetic analog of this peptide (synthetic neutrophil
inhibitor peptide, SNIP) on IL-8-induced nasal inflammation in humans, (2) effects of SNIP on PMN apoptosis and chemotaxis, (3)
specific binding of SNIP to PMNs, and (4) evidence of larger molecules with the SNIP sequence. Results show that SNIP attenuates
IL-8-induced nasal inflammation, inhibits in vitro PMN chemotaxis
to IL-8, and accentuates PMNs apoptosis. PMNs contain specific
SNIP-binding sites and the integrin CR3 (CD11b/CD18), or a CR3-associated molecule, is one SNIP-binding molecule. Chemotaxis to
IL-8 is most potently inhibited by SNIP in the presence of fibrinogen, a CR3 ligand. Antiserum against the SNIP sequence recognizes a 70-kDa protein in bronchoalveolar lavage and an anti-SNIP
immunoaffinity column binds a 70-kDa protein in U937 cell culture
supernatant. U937 cell mRNA contains a 1.8-kb transcript detected
with degenerate oligonucleotides designed from the SNIP sequence. These studies demonstrate that a synthetic inhibitor peptide can attenuate in vivo nasal inflammation through downregulatory effects on PMNs.
