Page 77 - Veterinary Immunology, 10th Edition

Tumor Necrosis Factor-α
VetBooks.ir TNF-α is a protein of 17 Da produced by sentinel cells in response

to TLR stimulation. TNF-α can also be produced by endothelial
cells, T cells, B cells, and fibroblasts. It is initially membrane-bound
but then cleaved from the cell surface by a protease called TNF-α

convertase. Soluble TNF-α triggers the release of chemokines and
cytokines from nearby cells and promotes the adherence, migration,
attraction, and activation of leukocytes (Fig. 3.1). Later, TNF-α
facilitates the transition from innate to adaptive immunity. TNF-α
production is stimulated not only through the TLRs but also by

molecules secreted by nerves such as the neurotransmitter
neurokinin-1.

FIG. 3.1 The origins and some of the biological activities of tumor
necrosis factor-α.

TNF-α is an essential mediator of inflammation because, in
combination with IL-1, it triggers changes in small blood vessels. A
local increase in TNF-α causes the classic signs of inflammation,

including heat, swelling, pain, and redness. Circulating TNF-α can
depress cardiac output, induce microvascular thrombosis, and
cause capillary leakage. TNF-α acts on neutrophils (key defensive
cells in inflammation; see Chapter 5) to enhance their ability to kill

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