Page 87 - Veterinary Immunology, 10th Edition

and large domestic herbivores. Serotonin normally causes a
VetBooks.ir vasoconstriction that results in a rise in blood pressure (except in

cattle, in which it is a vasodilator). It has little effect on vascular
permeability, except in rodents, in which it induces acute

inflammation.

Vasoactive Peptides

Vasoactive peptides are generated by proteolysis of inactive

precursors. For example, mast cell proteases act on the complement
component C5 to generate a small (15-kDa) peptide called C5a
(Chapter 4). This molecule promotes histamine release from mast
cells. C5a is also a potent attractant for neutrophils and monocytes.
Mast cell granules contain proteases called kallikreins. These act on

proteins called kininogens to generate small vasoactive peptides
called kinins. The most important of the kinins is bradykinin.
Kinins not only increase vascular permeability, they also stimulate

neutrophils and trigger pain receptors, and they may have
defensin-like antimicrobial activity. Neuropeptides such as
substance P and neurokinin produced by sensory nerves also cause
pain and trigger vasodilation and increased permeability. A peptide
called calcitonin gene-related peptide is the most abundant of these

neurotransmitters. It is a potent, painful vasodilator.

Vasoactive Lipids

When tissues are damaged or sentinel cells stimulated,

inflammasomes activate phospholipases that act on cell wall
phospholipids to produce arachidonic acid. The enzyme 5-
lipoxygenase then converts this arachidonic acid to biologically
active lipids called leukotrienes (Fig. 3.7). Another enzyme, called

cyclooxygenase, converts the arachidonic acid to a second family of
vasoactive lipids called prostaglandins. The collective term for all
these complex lipids is eicosanoids. They act as local inflammatory
hormones.

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