Biomedical Engineering Reference
In-Depth Information
Table 2
The Inhibitors of Neutrophil Proteinases
a
1
-AT Produced by liver and found in serum. Irreversibly inhibits free
NE, CG, and PR3 (203)
SLPI Produced by mucosal cells. Reversibly inhibits NE and CG (204)
a
2
-Macroglobulin Serum. Irreversibly inhibits all classes of proteinases (205)
Elafin
Produced from mucosal cells. Reversibly inhibits NE and PR3
(204)
Monocyte
=
NE
inhibitor
Produced from neutrophils and monocytes irreversibly inhibits
NE, CG, and PR3 (206)
II. NEUTROPHIL STRUCTURE AND DEVELOPMENT
The neutrophil originates from bone marrow where it develops from a bipo-
tential progenitor cell, the granulocyte-macrophage colony-forming unit.
Neutrophils have a characteristic multilobed nucleus and abundant storage
granules in their cytoplasm. The mature neutrophil has three chemically
distinct granule types, which appear at different stages of maturation. The
azurophilic (or primary) granules are formed early during the promyelocyte
stage and contain MPO, antibacterial proteins (such as defensins, lysozyme,
and azurocidin), and serine proteinases such as NE, cathepsin G
(CG) and proteinase 3 (PR3) (14). The proteinases are produced as pre-
proenzymes, with gene expression stopping at the metamyelocyte stage
(15), and are activated by a lysosomal cysteine proteinase, dipeptidyl pepti-
dase (16). The specific (or secondary) granules are formed later, during the
myelocyte stage and contain lysozyme, lactoferrin, and various membrane
receptors. The gelatinase-containing granules are formed last, at the meta-
myelocyte stage, and contain metalloproteinases.
These proteins provide the mechanisms of cell migration, opsonophago-
cytosis, and a formidable arsenal against pathogens to enable clearance of
cellular debris. The neutrophil proteinases (especiallyNE) also have the poten-
tial to be intensely destructive and are able to degrade structural lung proteins
(acting as elastases, collagenases, or gelatinases) and are involved in post-
translational processing of other enzymes, cytokines, and receptors (17).
Neutrophils leave the bone marrow fully matured and once activated
migrate into the connective tissue. Once in the tissue, apoptosis occurs on
average 8 hr after leaving the bone marrow (18).
III. PROMIGRATORY STIMULI
Neutrophils migrate into the lung in response to soluble mediators. Promi-
gratory stimuli can be classified as nonchemotactic cytokines, chemotactic
cytokines, or chemoattractants.
