Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 439

Table 8.26. Eicosanoids associated with blood circulation. ( Part 3 ) Lipoxins (CXCL: CXC
(C-X-C motif; ) chemokine ligand; TGF: transforming growth factor; TNF: tumor-necrosis

factor). The lipoxygenase pathway is active in leukocytes (basophils, eosinophils, neutrophils,
mastocytes, and monocytes). Synthesis of lipoxins from arachidonic acid occurs via cellular in-
teractions, using 3 pathways. The classical pathway involves 5-lipoxygenase (5LOx) in leukocytes
followed by 12LOx in platelets. In airway epithelial cells, 15LOx action is followed by that of
5LOx in leukocytes (second lipoxin synthesis pathway). In epithelial and endothelial cells as well
as monocytes, aspirin acts on COx2 to produce 15-epilipoxins.

α

Type Synthesis site Activity

LxA4 Platelet, endothelial cells, Reduction of granulocyte infiltration to

mucosal epithelial cells, inflammation sites,

and other leukocytes via monocyte recruitment,

interactions with granulocytes phagocytosis by macrophage

stimulation of TGF

,
repression of CXCL8 production,
inhibition of TNF

β

α release

LxB4 Platelet, endothelial cells, Reduction of granulocyte infiltration to

mucosal epithelial cells, inflammation sites,

and other leukocytes via monocyte recruitment,

interactions with granulocytes phagocytosis by macrophage

stimulation of TGF

,
repression of CXCL8 production,
inhibition of TNF

β

α release

hydroperoxyl radical (HO 2 ), among others. Reactive nitrogen species comprise
nitric nitrogen dioxide (NO 2 ), oxide (NO), dinitrogen trioxide (N 2 O 3 ), and

peroxynitrite (ONOO − ).
Anti-oxidants include enzymes, such as superoxide dismutase, catalase, glu-
tathione peroxidase, peroxiredoxins, heme oxygenase, glutaredoxin, and thiore-
doxin, and non-catalytic agents, such as glutathione, -carotene, retinol, and

vitamin-C and -E (Vol. 4 - Chap. 10. Other Major Signaling Mediators). 77
The first NOX group comprises NOx1 to NOx4; the second group DuOx1
and DuOx2; the third group NOx5 with its 4 splice variants (NOx5

β

α -NOx5 δ )

and a truncated isoform (NOx5 ). Most NOx enzymes are multisubunit enzymes

with cytochrome-B245, organizer, and activator components; in the absence of
stimulation, they are unassembled and inactive.
In airway epithelia, reactive oxygen species are mainly produced by dual
oxidases (DuOx1 and DuOx2) [ 816 ]. Their synthesis is regulated by cytokines. 78

77 Superoxide is dismuted to hydrogen peroxide by superoxide dismutase. This derived product
can be converted to water by catalase or glutathione peroxidase. Superoxide can also react with
nitric oxide to generate peroxynitrite that may be converted into nitrogen dioxide, which reacts
with tyrosine residues to generate NO 2 Tyr that limits NO availability.
78 Interleukin-4

and -13 produced by T H2 cells increase moderately DUOX1 transcription;

γ

interferon- produced by T H1 cells elevates markedly DUOX2 transcription.