Am. J. Respir. Cell Mol. Biol., Vol 15, No. 1, Jul 1996, 35-44.
TNF alpha is important in human lung allergic reactions
TB Casale, JJ Costa and SJ Galli
Department of Internal Medicine, VA Medical Center, Iowa City, Iowa, USA.
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.
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Copyright © 1996 American Thoracic Society.
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