Differential expression of the tumor necrosis factor/cachectin gene by blood and lung mononuclear phagocytes.

Publication Type	Academic Article
Authors	Martinet Y, Yamauchi K, Crystal R
Journal	Am Rev Respir Dis
Volume	138
Issue	3
Pagination	659-65
Date Published	09/01/1988
ISSN	0003-0805
Keywords	Gene Expression Regulation, Genes, Lung, Phagocytes, Tumor Necrosis Factor-alpha
Abstract	Tumor necrosis factor (TNF), also called cachectin, is a mononuclear phagocyte-derived mediator with a broad range of biologic activities contributing to antineoplastic and antiviral defenses as well as mediating a variety of processes associated with acute and chronic inflammatory states, including endotoxin-induced shock. To evaluate the relative capacity of human tissue macrophages to produce this mediator, alveolar macrophages and blood monocytes from the same normal individuals were activated with lipopolysaccharide (LPS) and evaluated for TNF release and TNF mRNA transcript levels. Resting alveolar macrophages did not express TNF mRNA transcripts or release TNF. However, when activated, alveolar macrophages expressed TNF transcripts and synthesized and released TNF as evidenced by the presence of a 28 kDa mediator in LPS-activated alveolar macrophage supernatants that had cytotoxic activity for L-929 cells that was abrogated by anti-TNF antibodies and that coeluted with a pure TNF standard on a molecular sieve column. Interestingly, activated alveolar macrophages released severalfold more TNF than did autologous blood monocytes stimulated in a similar fashion and, in parallel, the alveolar macrophages expressed more TNF mRNA transcripts than activated blood monocytes. Thus, the ability to express the TNF gene and to release TNF apparently increases during maturation of blood monocytes into alveolar macrophages, suggesting that the release of TNF in the local milieu by activated tissue macrophages may be much more significant than the release of this mediator by circulating blood monocytes.
DOI	10.1164/ajrccm/138.3.659
PubMed ID	3202418