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

Chapter 11
Neutrophil Function
Douglas J. Weiss
Department of Veterinary Pathobiology
College of Veterinary Medicine
University of Minnesota
St. Paul, Minnesota
Bruce Walcheck
Department of Veterinary and Biomedical Sciences
College of Veterinary Medicine
University of Minnesota
St. Paul, Minnesota
I. INTRODUCTION
II. NEUTROPHIL FUNCTIONS
A. Adherence and Chemoattractants
B. Phagocytosis
C. Bactericidal Mechanisms
D. Neutrophil-Mediated Amplification of
Inflammation
III. V IRULENCE FACTORS PREVENTING NEUTROPHIL-
MEDIATED KILLING
IV. ACQUIRED NEUTROPHIL FUNCTION DEFECTS
A. Neutrophil Dysfunction in Periparturient
Dairy Cattle
B. Neutrophil Dysfunction in Neonatal Animals
C. Neutrophil Dysfunction Associated with
Viral Infection
D. Effects of Nutrition on Neutrophil Function
E. Effects of Stress on Neutrophil Function
V. NEUTROPHIL-MEDIATED TISSUE INJURY
A. Neutrophil-Mediated Injury at Sites of
Inflammation
B. Ischemia/Reperfusion Injury
C. Neutrophil-Mediated Injury at Distant Sites
D. Role of Neutrophils in Microvascular
Thrombosis
REFERENCES
I . INTRODUCTION
Pluripotential hematopoietic stem cells in the bone marrow
differentiating in response to specific growth factors give
rise to committed progenitors and then neutrophils. These
cells are characterized by their multilobed nuclei and
abundant granules in the cytoplasm (polymorphonuclear
neutrophilic granulocytes). Except in disease states, only
functionally mature neutrophils are released into the
blood from the bone marrow, and these cells contain much
of their effector molecules prepackaged in cytoplasmic
granules or in the plasma membrane. Mature neutrophils
do not multiply but instead are continuously replaced.
Neutrophils circulate in the blood for only a few hours and
survive in the tissue for only a few days; however, this can
be extended by a day or two upon their exposure to various
activating agents at sites of inflammation. In any case,
neutrophils eventually succumb to programmed cell death
by an intrinsic or extrinsic apoptotic pathway. Once neutrophils
are recruited into the underlying tissue from the
blood and encounter a microorganism, they phagocytize
and kill the pathogen to eliminate the infection. This chapter
provides an overview of the mechanisms of neutrophil
adherence, chemotaxis, phagocytosis, and organism killing.
It also discusses congenital and acquired defects in neutrophil
function that predispose animals to infection. Finally,
this chapter discusses neutrophil-mediated tissue injury.
II . NEUTROPHIL FUNCTIONS
A . Adherence and Chemoattractants
1 . Overview
The recruitment of neutrophils to sites of tissue injury and
infection is a hallmark of the acute inflammatory response.
Efficient neutrophil extravasation at sites of inflammation
requires a coordinated cascade of adhesive and signaling
events. Neutrophils leave the flowing blood stream by
first tethering and then rolling on the inflamed endothelium
lining the blood vessel lumen. In the systemic circulation,
this occurs primarily as neutrophils enter the venule from
the capillaries (postcapillary venules) and in the collecting
venules ( Atherton, 1972 ; Schmid-Schonbein et al. , 1980 ).
With the appropriate chemoattractants, rolling neutrophils
will arrest (stop rolling) becoming firmly adherent to the
endothelial surface and then migrate across the endothelium.
Clinical Biochemistry of Domestic Animals, 6th Edition 331
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