Page 66 - Veterinary Immunology, 10th Edition

tissues such as the lung, where they release their proteases and
VetBooks.ir cause damage. Thus in animals with severe trauma, mitochondrial

DNA and formyl peptides are released from damaged tissues and
flood into the bloodstream. The resulting inflammatory cascade is

an initiating factor for the systemic inflammatory response
syndrome (Chapter 7).
One of the most important intracellular DAMPs is high mobility
group box protein-1 (HMGB1) (Fig. 2.8). HMGB1 normally binds

DNA molecules and ensures that they fold correctly. However,
HMGB1 is also a potent trigger of inflammation. It is secreted by
macrophages that have been activated by lipopolysaccharides or by
cytokines such as IFN-γ. HMGB1 also escapes from broken cells.

HMGB1 binds both TLR2 and TLR4 and sustains and prolongs
inflammation. It stimulates the secretion of inflammatory cytokines
from macrophages, monocytes, neutrophils, and endothelial cells.
Administration of HMGB1 to animals causes fever, weight loss,

anorexia, acute lung injury, arthritis, and even death. HMGB1
stimulates the growth of new blood vessels and tissue repair. It also
has potent antimicrobial activity. The cytokine IL-33 is also stored
within the nucleus and released when cells die (Chapter 29). It too

is a potent DAMP.

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