Cytokines

Cytokines

Handbook of Immunopharmacology
1998, Pages 335-360
Cytokines

24. - Tumor Necrosis Factor and Lymphotoxin

https://doi.org/10.1016/B978-012498340-3/50025-7Get rights and content

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Tumor necrosis factor (TNF) and lymphotoxin (LT) display a similar spectrum of activities in in vitro systems, although LT is often less potent or apparently has partial agonistic activity. Both TNF and LT genes are encoded by a single gene of about 3 kilobases (kb) in size. Mature secreted human TNF consists of 157 amino acids (aa), whereas human LT contains 171 residues. The mature LT protein is preceded by a “classical” 34-aa signal sequence, while the mature TNF is preceded by a 76-aa presequence, the first part of which corresponds to an intracellular domain when TNF is present as a 26 kDa membrane-bound form. The homology between LT and TNF at the aa level amounts to 28%. TNF or LT treatment of cells mediates an antiviral effect against several viruses, such as vesicular stomatitis virus (VSV) and herpes simplex-2 (HSV-2). TNF has also been shown to lyse cells infected with different viruses. However, TNF has been shown to enhance the infection rate and replication of human immunodeficiency virus (HIV). This enhancement is mediated by transcriptional upregulation of the HIV long terminal repeat as a result of TNF-induced activation of the transcription factor NFκB. Activated monocytes/macrophages are the major in vivo sources of endogenous TNF synthesis. TNF rapidly induces neutrophil adherence to endothelial cells, activates phagocytosis, and enhances specific antibody-dependent cellular cytotoxicity. TNF also increases adhesion of neutrophils to extracellular matrix proteins, such as fibrinogen, fibronectin, and even serum-coated plastic. This TNF-induced increase in adhesiveness is based on a conformational rearrangement of the CD11a/CD18 and CD11b/CD18 integrins on the cell surface.

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