Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 104

3.8.3.3 Arterial Wall Mastocytes

In normal arterial intima, only a few mastocytes are present (average density
∼ 50 cell/mm 2 )[ 198 ].

However, in atheroma, mastocytes, together with macrophages and T lymphocytes
invade the intima.

1 cell/mm 2 , i.e., much smaller density than that in skin

∼

3.8.3.4 Cardiac Mastocytes

Maturation of resident cardiac mastocytes is associated with formation of chymase
and histamine as well as the loss of division capacity. Four stages of mastocyte
maturation can be defined [ 200 ]: stage 1 in which immature cells have the smallest
size, 2 in which still immature cells are able to divide and possess granules, 3 in
which non-dividing cells are endowed with abundant granules, and 4 characterized
by fully differentiated, mature cells.
Cardiac mastocytes that synthesize, store, and release active renin trigger a
(non-kidney-derived) cardiac renin-angiotensin system. Local generation of cardiac
angiotensin-2 from mastocyte-derived renin causes noradrenaline secretion from
isolated sympathetic nerve terminals via AT 1 receptors [ 199 ].
Cardiac mastocytes synthesize various growth factors, cytokines, chemokines,
nitric oxide and other vasoactive molecules, peptidases, fatty acid metabolites,
and other mediators involved in tissue remodeling. Mastocytes store and release
several agents that can activate matrix metallopeptidases that degrade the collagen
matrix [ 200 ].
Mastocyte peptidases, such as chymase and tryptase, can activate zinc-dependent
interstitial collagenase-1 (MMP1), gelatinases (MMP2), and stromelysin (MMP3).
Matrix metallopeptidases are produced and released as inactive zymogens;
their propeptide domain is removed to obtain an active enzyme. Chymase activates
proMMP1; tryptase cleaves proMMP3. Peptidase MMP3 then activates other
proMMPs, in particular, activating MMP1 enzyme. In addition, mastocytes
can synthesize and secrete MMP1 peptidase. Moreover, chymase and tryptase
degrade fibronectin and vitronectin. Chymase is also capable of cleaving inactive
angiotensin-1 to active angiotensin-2. In addition, mastocytes produce TNF

α that

activate MMP9 synthesized from themselves and adjacent macrophages.
Identified secretagogues encompass endothelin-1, reactive oxygen species,
interleukin-33, complement factor-5A, and several neuropeptides [ 200 ]. Endothelin-
1 operates via its ET A receptor and activates cardiac mastocytes. Reactive oxygen
species (oxidative stress) can induce mastocyte degranulation. Interleukin-33, a
member of the IL1 family of cytokines, regulates mastocyte function.
The complement molecule, C5a, a proteic fragment released from complement
component C5, is a chemoattractant for mastocytes, an anaphylatoxin that causes
histamine release from mastocytes, and a potent inflammatory mediator. It binds to
a Gi-coupled receptor (C5aR or CD88) of target cells such as granulocytes.