Biomedical Engineering Reference
In-Depth Information
monocytes, and lymphocytes. Inflammatory cells, once recruited in the air-
space become activated and generate ROS in response to inflammatory
mediators. The activation of macrophages, neutrophils, and eosinophils
generates O
2
-
, which is rapidly converted to H
2
O
2
under the influence of
superoxide dismutase (SOD), and
OH is formed non-enzymatically in the
presence of Fe
2
þ
as a secondary reaction. ROS and reactive nitrogen species
(RNS) can also be generated intracellularly from several sources such as
mitochondrial respiration, the NADPH oxidase system, and xanthine
=
xanthine oxidase (Fig. 3). However, the primary ROS-generating enzyme
is NADPH oxidase, a complex enzyme system that is present in phagocytes
and epithelial cells.
In addition to NADPH oxidase, phagocytes employ other enzymes to
produce ROS, which involves the activity of heme peroxidases (myeloperox-
idase, MPO) or eosinophil peroxidase (EPO). Activation of EPO results in
the formation of the potent oxidant hypochlorous acid (HOCl) and hypo-
bromous acid (HOBr) from H
2
O
2
in the presence of chloride (Cl
) and bro-
mide (Br
) ions, respectively (Fig. 4). It is believed that the oxidant burden
produced by eosinophils is substantial because these cells possess several
times greater capacity to generate O
2
-
and H
2
O
2
than neutrophils, and
the content of EPO in eosinophils is 3-10 times higher than the amount
of MPO present in neutrophils (10).
Figure 3
Cellular generation of NO-derived ROS and RNS. Intracellular reactive
oxygen species O
2
¼
superoxide anion, NO
¼
nitric oxide, H
2
O
2
¼
hydrogen per-
oxide, OH
¼
hydroxyl radical, NO
2
¼
nitrogen dioxide, ONOO
¼
peroxynitrite.
