Analysis of recombinant human tumour necrosis factor-alpha-induced CD4 expression on human eosinophils.
We examined the hypothesis that one of the pro-inflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha), could induce expression of the adhesion molecule CD4 on human eosinophils. We further examined the effector function of CD4 and the mechanisms regulating CD4 expression. Human eosinophils were cultured with various concentrations of recombinant human TNF-alpha (rhTNF-alpha) with or without various drugs for 24 hr. After culture, eosinophils were stained for CD4 using a monoclonal antibody and then analysed by flow cytometry. Eosinophil-derived neurotoxin (EDN) release as eosinophil degranulation was examined by cross-linking of CD4 on eosinophils. The rhTNF-alpha induced CD4 expression on human eosinophils in a dose- and time-dependent fashion; rhTNF-alpha-induced CD4 expression was significantly inhibited by 10(-6) M cycloheximide, 10(-8) M dexamethasone, or 10(-6) M herbimycin A. Recombinant human interferon-gamma inhibited rhTNF-alpha-induced CD4 expression in a dose-dependent manner. However, cross-linking of CD4 on eosinophils did not evoke EDN release, suggesting that newly expressed CD4 molecules on human eosinophils do not play any role in triggering degranulation. Our data indicate that TNF-alpha-induced CD4 expression on human eosinophils is dependent on protein synthesis and may be dependent on tyrosine kinase activity.
Hossain
M
M
First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Okubo
Y
Y
Horie
S
S
Sekiguchi
M
M
D016227:Benzoquinones; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism*; D015550:Cell Degranulation; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016227:Benzoquinones; D015704:CD4 Antigens; D047029:Lactams, Macrocyclic; D011500:Protein Synthesis Inhibitors; D011809:Quinones; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D017828:Rifabutin; C020754:herbimycin; D003907:Dexamethasone; D007371:Interferon-gamma; D003513:Cycloheximide; D011505:Protein-Tyrosine Kinases