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TNF alpha is important in human lung allergic reactions.

Abstract：

:Tumor necrosis factor alpha (TNF alpha) is a potentially important cytokine in allergic respiratory reactions since it is released by mast cells and eosinophils, and it can promote mediator and cytokine release, adhesion molecule expression, and granulocyte migration. Therefore, we induced an IgE-mediated response in human lung samples and studied: (1) whether TNF alpha was produced in sufficient quantities to promote granulocyte migration; and (2) which cells expressed mRNA for TNF alpha using in situ hybridization. Lung fragments (from thoracotomy) were treated for 30 min with either anti-IgE, 1:100 dilution, or buffer (control). Anti-IgE treatment of 16 lungs resulted in greater than 4-fold increase in histamine release and the significant production of chemotactic activity. The chemotactic activity generated induced dose-responsive neutrophil and eosinophil migration through naked filters and endothelial and pulmonary epithelial monolayers. Fourteen of 16 samples had a significant increase in TNF alpha subsequent to anti-IgE treatment (P < 0.05). Anti-TNF alpha antibody (4 micrograms/ml) inhibited about 25% of the neutrophil chemotactic activity in supernatants from anti-IgE treated lungs. TNF alpha at a concentration measured after anti-IgE treatment of lung samples (50 pg/ml) induced neutrophil transendothelial migration. Finally, we found that anti-IgE treatment led to an increase in TNF alpha mRNA-positive cells by in situ hybridization (1.6/ mm2 experimental versus 0.5/mm2 control), some of which were eosinophils. Thus, human lung IgE-mediated responses in vitro results in: (1) release of TNF alpha in amounts sufficient to effect a biologic response, granulocyte chemotaxis: and (2) upregulation of mRNA for TNF alpha in eosinophils and other cells. These findings suggest that TNF alpha is an important effector molecule in the pathogenesis of allergic respiratory reactions.

journal_name

Am J Respir Cell Mol Biol

journal_title

American journal of respiratory cell and molecular biology

authors

Casale TB,Costa JJ,Galli SJ

doi

10.1165/ajrcmb.15.1.8679220

subject

Has Abstract

pub_date

1996-07-01 00:00:00

pages

35-44

issue

eissn

1044-1549

issn

1535-4989

journal_volume

pub_type

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TNF alpha is important in human lung allergic reactions.