CD44
Neutrophils are important phagocytotic
leukocytes (white blood cells) that internalize and destroy infectious bacteria
by a respiratory burst of reactive oxygen species and by enzymatic digestion.
Along with macrophages, neutrophils are crucial phagocytotic cells of the immune system and also contribute
to anti-viral defenses, binding to and eliminating free virus or virus-infected
cells. The presence of cytoplasmic granules in neutrophils leads to their classification as granulocytes,
along with basophils and eosinophils.
A lack of neutrophils or their normal function causes
a variety of immune disorders and measuring neutrophil
cell surface proteins can diagnose abnormal immune function. One such disorder
is caused by a lack of normal expression of the adhesion molecules CD11 and CD18
by neutrophils, preventing them from interacting
normally with adhesion molecules on endothelial cells and migrating into
inflamed sites in tissues. CD11a and CD18 together form the LFA-1 receptor for
ICAM-1 on endothelial cells and CD11b/CD18 form Mac-1. Deletion of the CD18
gene in mice produces a significant reduction in leukocyte emigration to sites
of inflammation. CD44 is involved in the interaction of neutrophils
with endothelial cells and the extracellular matrix
during inflammation. The binding of selectins with
their carbohydrate ligands also regulates adhesion of
neutrophils with endothelial cells, with P- and L-selectins moderating initial interactions and E-selectin moderating subsequent interactions. Genetic
disruption of the ability of neutrophils to kill
internalized bacteria also impairs normal immune function, along with genetic
or acquired lack of the normal number of neutrophils
(neutropenia). CD11b binding to a complement
component and CD16 binding to IgG Fc
contribute to phagocytosis. Inflammatory cytokines
activate neutrophils and chemotactic
peptides attract them to sites of infection. Inflammatory molecules that
activate neutrophils include IL-1, TNF, IL-6,
C-reactive protein, C3a and C5a complement anaphylatoxins,
leukotrienes, PAF, and histamine. Inappropriate
recruitment and activation of neutrophils and the
release of reactive oxygen species can damage surrounding tissues in
inflammatory conditions including arthritis and reperfusion of heart tissue
following myocardial infarction