Attenuation of interleukin 8-induced nasal inflammation by an inhibitor peptide.
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.
Cooper
J A
JA
Pulmonary Sections, Birmingham Veterans Affairs Medical Center, and University of Alabama at Birmingham, Birmingham, Alabama, USA.
Ridgeway
A L
AL
Pearson
J
J
Culbreth
R R
RR
D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000302:isolation & purification; D015536:Down-Regulation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D012220:Rhinitis / Q000276:immunology*; D020539:Sequence Analysis, Protein
D002352:Carrier Proteins; D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D010455:Peptides