Stimulation of neutrophil interleukin-8 production by eosinophil granule major basic protein.
We evaluated the ability of eosinophil granule major basic protein (MBP) to stimulate interleukin (IL)-8 production by neutrophils. MBP over the concentration range of 0.1 to 10 microM stimulated the release of up to approximately 8 ng/ml IL-8. Incubation with 2 microM MBP showed that, after a 1 h lag, the level of IL-8 release increased with time for approximately 10 h. At the 2 microM concentration, eosinophil cationic protein, eosinophil-derived neurotoxin, and eosinophil peroxidase did not stimulate significant levels of IL-8 production. MBP stimulated 2-fold increases in IL-8 messenger RNA (mRNA) after 1 and 3 h of incubation, which were blocked by pretreatment with actinomycin D. However, stimulation with MBP did not produce an increase in the binding activity of nuclear factor (NF)-kappaB or activator protein-1. No NF-IL-6 binding activity was detected in the same nuclear extracts. In addition, stimulation with MBP prolonged the stability of IL-8 mRNA. MBP also induced transient increases in mRNA for macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, but did not stimulate the release of either chemokine. These findings indicate that MBP is selective among the eosinophil granule proteins as a stimulus for neutrophil IL-8 release and, further, that stimulation of neutrophil IL-8 release by MBP involves both transcriptional and posttranscriptional regulation. We postulate that MBP-induced release of IL-8 by neutrophils may contribute to the pathophysiology of acute asthma and other inflammatory lung diseases.
Page
S M
SM
Department of Immunology/Microbiology, Rush Medical College, Chicago, Illinois, USA.
Gleich
G J
GJ
Roebuck
K A
KA
Thomas
L L
LL
D001798:Blood Proteins / Q000378:metabolism / Q000494:pharmacology*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D047091:Eosinophil Granule Proteins; D047208:Eosinophil-Derived Neurotoxin; D004804:Eosinophils / Q000378:metabolism; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000097:blood; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D012260:Ribonucleases; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic
D001798:Blood Proteins; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D047091:Eosinophil Granule Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B; D011506:Proteins; D018808:Transcription Factor AP-1; D003609:Dactinomycin; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases