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

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IV. Acquired Neutrophil Function Defects<br />

341<br />

insertion <strong>of</strong> a polyethylene intramammary device into the<br />

gland cisterns increased the somatic cell count and resulted<br />

in a 75% reduction in clinical mastitis ( Goodger et al. ,<br />

1993 ). Additionally, intramammary administration <strong>of</strong> soluble<br />

CD14 in coliform mastitis causes binding <strong>of</strong> endotoxin<br />

and results in recruitment <strong>of</strong> neutrophils.<br />

Genetic markers have also been associated with susceptibility<br />

to bovine mastitis. Cows with allelic variation in<br />

CXCR2 (i.e., the IL-8 receptor) had increased susceptibility<br />

to mastitis (Rameaud and Pighetti, 2005). Cows with a CC<br />

or GC at CXCR2 777 had decreased neutrophil migration<br />

in response to IL-8 when compared to cows expressing the<br />

GG genotype. Additionally, decreased up-regulation <strong>of</strong> cell<br />

surface CD18 was observed on neutrophils after stimulation<br />

with IL-8. The results <strong>of</strong> these studies support a genetic predisposition<br />

to mastitis and further emphasize the importance<br />

<strong>of</strong> rapid mobilization <strong>of</strong> neutrophils into the mammary gland<br />

in prevention <strong>of</strong> infection.<br />

B . Neutrophil Dysfunction in Neonatal<br />

<strong>Animals</strong><br />

Neutrophil dysfunction appears to contribute to the susceptibility<br />

<strong>of</strong> newborn calves and foals to pneumonia, septicemia,<br />

enteritis, and endotoxemia. Reports on neutrophil function<br />

in calves tend to be inconsistent. This is in part due to variation<br />

in the age <strong>of</strong> the calves, the colostrum status, and the<br />

techniques used to evaluate neutrophil function. For example,<br />

both increased and decreased respiratory burst activity<br />

have been reported in neonatal calves when compared to<br />

adult cows ( Dore et al. , 1991 ; Higuchi and Nigahata, 1998).<br />

Respiratory burst activity in neonates is dependent on the<br />

agonist used. Respiratory burst activity appears to be reduced<br />

when neonatal neutrophils are activated by heat-aggregated<br />

albumin or protein kinase C and enhanced when activated by<br />

opsonized zymosan. This suggests age-related alterations in<br />

cell membrane receptors or differences in intracellular signal<br />

transduction probably involving protein kinase C activity<br />

and tyrosine phosphorylation <strong>of</strong> cellular proteins (Higuchi<br />

and Nigahata, 1998). Other functional alterations in neonatal<br />

neutrophils when compared to adult neutrophils include<br />

decreased myeloperoxidase and increased alkaline phosphatase<br />

activities, decreased concanavalin A capping, decreased<br />

Fc receptor number, increased chemotaxis, increased aggregation,<br />

and increased shape change ( Zwahlen et al. , 1992 ).<br />

Reports <strong>of</strong> neutrophil dysfunction in foals are also somewhat<br />

inconsistent. When compared to adult horses, some<br />

reports indicate that foals have no difference in phagocytic<br />

activity, others report decreased phagocytosis when organisms<br />

are opsonized with autologous serum but not when opsonized<br />

with adult serum, whereas yet others state that phagocytosis <strong>of</strong><br />

Staphylococcus aureus is decreased when opsonized with<br />

either autologous or adult serum ( McTaggart et al. , 2001 ).<br />

Bacterial killing has been reported to be similar to that <strong>of</strong><br />

adult horses in several studies but was found to be reduced in<br />

other studies ( Wichtel et al. , 1991 ). Other neutrophil function<br />

alterations reported in foals include increased random migration,<br />

decreased chemotaxis, decreased iodination, increased<br />

CD18 expression, and the presence <strong>of</strong> an unidentified serum<br />

factor that suppresses oxidative burst activity.<br />

C . Neutrophil Dysfunction Associated with<br />

Viral Infection<br />

Viral infections have frequently been incriminated as predisposing<br />

food animals to bacterial infections. This effect may,<br />

in part, be mediated by virus-induced neutrophil dysfunction.<br />

The bovine viral diarrhea (BVD) virus is a classic example<br />

<strong>of</strong> a virus that induces neutrophil dysfunction ( Brown et al. ,<br />

1991 ; Roth et al. , 1981 ). Neutrophils from cows experimentally<br />

infected with cytopathogenic or noncytopathogenic<br />

strains <strong>of</strong> BVD developed marked impairment <strong>of</strong> iodination<br />

capacity. Alternatively, other measures <strong>of</strong> oxygen radical<br />

generation were not altered. Cattle that were persistently<br />

infected with BVD had multiple alterations in neutrophil<br />

function including decreased random migration, decreased<br />

Staphylococcus aureus ingestion, decreased cytochrome<br />

C reduction, decreased iodination, decreased antibodyindependent<br />

cell-mediated cytotoxicity, decreased cytoplasmic<br />

calcium flux, and decreased oxygen radical production.<br />

Another virus incriminated as predisposing cattle to<br />

bacterial pneumonia is infectious bovine rhinotracheitis<br />

(IBR) virus ( McGuire and Babiuk, 1983/1984 ). In an<br />

in vivo study, calves were exposed to an aerosol <strong>of</strong> IBR<br />

virus and then to an aerosol <strong>of</strong> Mannheimia haemolytica<br />

5 days later. When compared to calves not exposed to IBR<br />

virus, IBR-exposed calves had delayed neutrophil migration<br />

into the lungs. Neutrophils from IBR-exposed calves<br />

also had decreased random migration and chemotactic<br />

responses. Further, alveolar macrophages had decreased<br />

capacity to produce chemotactic factors. The results <strong>of</strong> this<br />

study indicate that IBR infection may predispose cattle to<br />

secondary bacterial infections.<br />

Neutrophil function has also been investigated in cats<br />

infected with feline leukemia virus ( Kiehl et al. , 1987 ).<br />

Neutrophil chemotaxis was evaluated in vitro by use <strong>of</strong> a<br />

modified Boyden chamber apparatus. Cats that were viremic<br />

and clinically ill had lower chemotactic responses<br />

compared to subclinically infected cats. This did not appear<br />

to be a nonspecific effect in that cats that were sick from<br />

other causes did not have reduced chemotactic responses.<br />

D . Effects <strong>of</strong> Nutrition on Neutrophil<br />

Function<br />

Selenium and vitamin E appear to be important nutrients<br />

in maintaining neutrophil function. As stated previously,

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