Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 11 Neutrophil Function
The observation that blood flow to an ischemic organ is not
fully restored after release of a vascular occlusion has been
termed the no-reflow phenomenon. Experimental studies,
using leukocyte depletion models, have demonstrated a
central role of neutrophils in the no-reflow phenomenon.
C . Neutrophil-Mediated Injury at
Distant Sites
Neutrophils become activated within the circulation during
a variety of physiological and pathological conditions
in domestic animals. Circulating activated neutrophils have
been documented during strenuous exercise, inflammatory
disease, equine colic, and equine laminitis. At least in
some circumstances, there is evidence to suggest that these
activated neutrophils may contribute to the pathogenesis of
the disease process.
1 . Exercise
Strenuous exercise has been associated with up-regulation
of neutrophil surface-associated integrin receptors in dogs
undergoing short duration sled-pulling activity ( Moritz
et al. , 2003 ). Additionally, decreased neutrophil granularity
was observed postexercise. Because CD11b/CD18 integrin
is stored in neutrophil granules and transported to the cell
surface when neutrophils degranulate, the combination of
increased cell surface integrin concentration and decreased
granularity postrace is consistent with exercise-associated
neutrophil degranulation.
2 . Infl ammatory Disease
Neutrophils circulate in an activated state in a variety of
inflammatory conditions. Dogs with naturally occurring
septic and nonseptic inflammatory diseases had increased
cell surface expression of CD11b ( Weiss et al. , 2004 ).
Neutrophils from dogs with septic inflammatory diseases
and those with evidence of multiple organ dysfunction also
had decreased neutrophil granularity and increased neutrophil
size. However, neutrophil activation markers may
not predict neutrophil function. In a study by Gosset et al.
(1983/1984) , neutrophils from dogs with severe inflammatory
disease were reported to have a defect in bactericidal
activity. Monocytes and lymphocytes from dogs with septic
and nonseptic inflammation and multiple organ dysfunction
had decreased expression of major histocompatibility
factor class-II suggesting impaired immune responsiveness
( Weiss et al. , 2004 ).
Leukocyte deformability, neutrophil CD11b expression,
and neutrophil size were evaluated in calves experimentally
inoculated intrabronchially with Mannheimia haemolytica
organisms ( McClenahan et al. , 1999 ). Infected calves had
decreased leukocyte deformability and increased neutrophil
size by 1h and increased CD11b expression by 6h after
organism inoculation. Decreased neutrophil deformability
and increased size may contribute to sequestration of neutrophils
in alveolar capillary beds during sepsis.
3 . Colic
The activation status of circulating neutrophils was evaluated
in horses with naturally occurring colic ( Weiss and
Evanson, 2003 ). Activated neutrophils were not detected
in healthy horses or horses with impaction or gas colic.
Conversely, horses with inflammatory bowel disease consistently
had increased neutrophil cell membrane CD11/
CD18 expression, increased neutrophil size, and decreased
neutrophil granularity consistent with circulating activated
and degranulated neutrophils. These horses also had
decreased leukocyte deformability indicating that neutrophils
were rigid. Horses with strangulating colic had
variable results. Among horses with strangulating colic,
changes in leukocyte deformability, neutrophil size, and
neutrophil granularity correlated directly with adverse
outcome.
4 . Equine Laminitis
Neutrophils may become activated in the prodromal stages
of equine laminitis. At various times during the first 12 h
after induction of black walnut-induced laminitis, horse
neutrophils had increased oxygen radical production, and
some horses had increased phagocytosis of bacteria ( Black
et al. , 2006 ). These changes were associated with neutropenia
and were presumed to be due to a systemic inflammatory
response resulting from absorption of inflammatory
mediators from the intestine. These activated neutrophils
have been incriminated in the pathogenesis of the laminar
injury ( Black et al. , 2006 ).
5 . Adult Respiratory Distress Syndrome and Multiple
Organ Failure
A ctivated neutrophils are central to the pathogenesis of
ARDS and MODS associated with sepsis and endotoxemia
(Lehr et al. , 2000 ). As in ischemia/reperfusion injury, microvascular
injury is a major site of injury in these conditions.
The lungs are particularly sensitive to neutrophil-induced
vascular injury. The process of lung involvement has been
divided into four sequential stages: (1) sequestration of neutrophils
in pulmonary capillaries, (2) adhesion, (3) activation,
and (4) release of oxygen radicals and proteases ( Lee
and Downey, 2001 ). The process of neutrophil sequestration
in the lungs differs from that of other tissues. In other tissues,
neutrophil sequestration occurs predominately in postcapillary
venules and is dependent on selectin and integrin
adhesion molecules. Alternatively, neutrophil sequestration
in the lungs occurs primarily in pulmonary capillaries and
is largely independent of adhesion molecules. Sequestration