Page 141 - Veterinary Immunology, 10th Edition

Activation
VetBooks.ir Neutrophils must be activated before they attack and destroy

invaders. Thus, when neutrophils bind to endothelial cell integrins

and are stimulated by CXCL8 or C5a, they secrete elastase,
defensins, and oxidants. The elastase promotes their adhesiveness.
The oxidants activate tissue proteases, which in turn release TNF-α
from macrophages. The TNF-α, in turn, attracts more neutrophils,

thus providing feedback amplification.

Chemotaxis

Neutrophils crawl directly toward invading organisms and

damaged tissues attracted by chemotactic molecules. These
chemoattractants diffuse from sites of microbial invasion and form
a gradient. Neutrophils crawl toward the area of highest
concentration—the source of the material. The moving cells
generate projections (lamellipodia) at their leading edge.

Chemoattractant receptors are distributed over the neutrophil
surface, but the formation of lamellipodia is driven by the higher
concentration of attractants at the cell's leading edge.

Microbial invasion and tissue damage generate many
chemoattractants. These include the complement peptide C5a
(Chapter 4); a peptide called fibrinopeptide B, derived from
fibrinogen; and hydrogen peroxide. A damage-triggered gradient
of H O is established within 5 minutes of wounding, just preceding
2 2
the movement of the first neutrophils toward a wound. Other
attractants include chemokines, cathelicidins, and lipids such as

leukotriene B (Chapter 3). Invading bacteria release peptides with
4
formylated methionine groups that are very attractive to the
neutrophils of some mammals. Thus migrating neutrophils receive

a multitude of signals, causing them to swarm toward sites of
invasion and tissue damage in large numbers.
Some cattle with a specific genotype of the chemokine receptor

CXCR2 have reduced neutrophil migration compared with normal
cattle. Cows with this genotype also have reduced expression of the
integrin chains CD18 and CD11b and as a result have decreased
resistance to bacterial mastitis.

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