Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 105

Among neuropeptides, substance-P, which is released predominately from
afferent fibers of the sympathetic nervous system, provokes degranulation of cardiac
mastocytes. Neurotensin, which is produced in nerve fibers of the intracardiac
ganglia and coronary vasculature, as well as those that innervate cardiomyocytes and
nodal cells, also causes a calcium-dependent degranulation of cardiac mastocytes,
in addition to its positive inotropic effects mediated by noradrenaline release.
Cardiac mastocyte density rises in the left ventricle maladaptive hypertrophy
(e.g., upon mitral regurgitation [mitral insufficiency or incompetence]) that provokes
congestive heart failure. The myocardial MMP2 activity elevates with subsequent
collagen degradation [ 200 ].
Cardiac mastocytes are also involved in fibrosis developed in maladaptive
hypertrophy caused by arterial hypertension. Mastocyte density is correlated to
stem cell factor and SCFR receptor levels. Mastocytes can prevent macrophage
recruitment [ 200 ]. Mastocytes regulate fibrosis that results from pressure overload
via inflammatory cell recruitment and direct action on fibroblasts.
Mastocytes participate with monocytes, macrophages, and lymphocytes in in-
flammation during atherosclerosis. They can provoke plaque destabilization with
increased risk of rupture, in addition to their role in the development of aortic
abdominal aneurysms.
Cardiac mastocyte density also augments during myocardial infarction, in partic-
ular during the healing phase [ 200 ]. Recruited macrophages and neutrophils gather
near degranulated mastocytes. Mastocytes release renin and chymase that form
myocardial angiotensin-2. The latter elevates noradrenaline levels, hence risk of
arrhythmias. Renin and noradrenaline release indeed prime ventricular fibrillation
during ischemia-reperfusion events. Mastocytes also contribute to the regulation of
myofibroblast activity.

3.8.3.5 Airway Wall Mastocytes

Human lung mastocytes that reside predominantly in the submucosal connective
tissue of normal human bronchi synthesize renin that triggers angiotensin formation
after degranulation in airways [ 201 ]. Local generation of angiotensin-2 from mas-
tocyte renin primes contraction of bronchial smooth myocytes via AT 1 receptors. 92
The airway renin-angiotensin system thus complements the traditional, circulating
renin-angiotensin axis, in which renin is released into the blood circulation from
the kidneys in response to decreased renal perfusion pressure, reduced delivery of
NaCl at the macula densa, and/or increased renal sympathetic nerve activity. The
pulmonary endothelium is the primary source of angiotensin-converting enzyme in
the body.
In allergic asthma, mastocytes release renin, histamine, -hexosaminidase,

tryptase, leukotrienes LTc4 and LTd4, adenosine, cytokines, and kinins that elicit
acute and chronic airway constriction and inflammation.

β

92 Receptors AT 1 (or AT1R) and AT 2 (or AT2R) reside primarily on bronchial smooth myocytes
and bronchial epithelial cell brush border, respectively.