Production of tumor necrosis factor with IgE receptor triggering from sensitized lung tissue.
Mast cells and basophils have been known to play a central role in allergic inflammation through the release of chemical mediators by cross-linkage of IgE receptors. The IgE receptor triggering and calcium ionophore A23187 have also been shown to induce gene expression and production of tumor necrosis factor (TNF) by rat basophilic leukemia cells. In the present study, we examined whether IgE receptor triggering could induce gene expression and production of TNF in rat lung tissue. The lung tissue released not only histamine but also cytotoxic activity on L929 cells 2 and 4 h after incubation with dinitrophenyl conjugated to ovalbumin (DNP-OVA) following passive sensitization with anti-DNP monoclonal rat IgE antibody, whereas neither DNP-OVA nor anti-DNP IgE antibody could induce the cytotoxic activity when used solely. Calcium ionophore A23187 also could induce both histamine release and cytotoxic activity. These activities induced by IgE receptor triggering, A23187, and lipopolysaccharide were completely neutralized by preincubation with anti-mouse TNF-rabbit serum, but not with normal rabbit serum. Northern blot analysis using cDNA probe of mouse TNF demonstrated expression of TNF gene as early as 2 h after IgE receptor triggering. These data demonstrating that IgE receptor triggering induced gene expression and production of TNF in lung tissue suggest the participation of TNF in the pathogenesis of late asthmatic response through its biologic activities such as the attraction and activation of neutrophils and eosinophils.
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
I
I
Ohno
Y
Y
Ohkawara
K
K
Yamauchi
Y
Y
Tanno
T
T
Takishima
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D015152:Blotting, Northern; D046508:Culture Techniques; D015870:Gene Expression; D006636:Histamine Release; D007116:Immunization, Passive; D007073:Immunoglobulin E / Q000276:immunology*; D008168:Lung / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D011961:Receptors, Fc / Q000502:physiology*; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D000944:Antigens, Differentiation, B-Lymphocyte; D012333:RNA, Messenger; D011961:Receptors, Fc; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E