Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 399

8.4.5 Hyperresponsiveness and Hypersensitivity

Asthma is characterized by hyperplasia and hypertrophy of airway smooth myocytes
that strongly (hyperresponsiveness) contract in response to low-magnitude stimuli
(hypersensitivity), in addition to tissue inflammation with edema and thickening of
the subepithelial basement membrane. Both wall edema and bronchoconstriction
narrow lumens of ventilatory ducts, thereby reducing air flow as demonstrated
by lung function tests. Smooth myocytes colocalize with mastocytes. In addi-
tion, released interleukin-8 is a chemoattractant for neutrophils and eosinophils.
Mastocytes do not affect the rate of proliferation, but prevent CCL11-mediated
CCR3-primed migration of airway smooth myocytes [ 736 ].
Basement membrane thickening is due to the deposition of interstitial collagen-
1, -3, and -5 as well as fibronectin. Collagens are synthesized by myofibroblasts,
the number and activity of which rise in asthma due to fibroblast (FGF2), insulin-
like (IGF1), dimeric platelet-derived (PDGFbb), and transforming (TGF

β )growth

factor, as well as endothelin-1 [ 737 , 738 ].
Airway smooth myocytes contribute to the pathogenesis of asthma because
of [ 739 ]: (1) proliferation beyond the ordinary rate provoked by mitogens and
(2) recruitment of progenitors to airway smooth myocyte bundles, thereby causing
hyperplasia in addition to hypertrophy; (3) interactions of airway SMCs with
inflammatory cells, such as T lymphocytes and eosinophils; and (4) their secretion
of pro-inflammatory cytokines, in particular chemokines (Table 8.5 ). 26
Sphingosine 1-phosphate operates as an inflammatory mediator in asthma.
It provokes airway smooth muscle contraction and growth as well as production
of pro-inflammatory cytokines such as interleukin-6 to trigger bronchoconstriction
and airway inflammation and remodeling [ 740 ].

8.4.6 Deep Inspiration as Bronchodilation Inducer

Deep inspiration stretches airway smooth myocytes, thereby softening, or fluidizing
the cytoskeleton, especially stress fibers. Rapid fluidization followed by a slow
resolidification enables cells to reorganize their stress fibers and adhesion plaques in
response to mechanical stresses [ 741 ]. Resulting heightened mobility of cytoskele-
ton constituents and partners generates a significant bronchodilation.
In asthma, this phenomenon disappears due to remodeling of the cytoskeleton
and surrounding matrix [ 741 ]. However, in an acute, mild asthma attack, bron-
chospasm can be counteracted by a slow, complete inspiration. Deep inspirations

26 Bradykinin,

an asthmatic mediator, stimulates cyclooxygenase COx2 that produces

prostaglandin-E2. The latter causes interleukin-8 release [ 731 ].