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mast cell tryptase 481 Masugi nephritis
Glomerular
epithelial
cell
GBM
large vessels, mast cells are elongated. In loose connective
tissue, they are round or oval; their shape in fibrous connective
tissue may be angular. On their surfaces, they have
Fc receptors for immunoglobulin E (IgE). Cross linking by
either antigen for which the IgE Fab regions are specific or
by anti-IgE or antireceptor antibody leads to degranulation
with the release of pharmacological mediators of immediate
hypersensitivity from their storage sites in the mast cell
granules. Leukotrienes, prostaglandins, and platelet-activating
factor are also produced and released following Fcε
receptor cross linking. Mast cell granules are approximately
0.5 μm in diameter and are electron-dense. They contain
many biologically active compounds, of which the most
important are heparin, histamine, serotonin, and a variety
of enzymes. Histamine is stored in the granule as a complex
with heparin or serotonin. Mast cells also contain proteolytic
enzymes such as plasmin and hydroxylase, β glucuronidase,
phosphatase, and a high uronidase inhibitor, to mention only
the most important. Zinc, iron, and calcium are also found.
Some substances released from mast cells are not stored in
a preformed state but are synthesized following mast cell
activation. These represent secondary mediators as opposed
to preformed primary mediators. Mast cell degranulation
involves adenylate cyclase activation with rapid synthesis of
cyclic AMP, protein kinase activation, phospholipid methylation,
and serine esterase activation. Mast cells of the gastrointestinal
and respiratory tracts that contain chondroitin sulfate
produce leukotriene C 4, whereas connective tissue mast cells
that contain heparin produce prostaglandin D 2.
mast cell tryptase
A serine protease present in secretory granules of mast cells
and released with histamine during mast cell activation.
Serum tryptase is a clinical indicator of diseases of mast
cell activation such as systemic anaphylaxis or mastocytosis.
Tryptase is a better in vitro marker of anaphylaxis than
histamine because it has a slower release and is more stable.
The half-life of tryptase is 90 minutes. It takes at least 15
minutes to reach detectable concentrations. The best time to
measure tryptase is 1 to 2 hours but not more than 6 hours
after the reaction. In anaphylaxis, both α and β tryptase are
elevated. Most studies indicate that tryptase is increased
in postmortem blood following severe anaphylaxis and is a
reliable postmortem indicator of fatal anaphylaxis.
Ag
Endothelium
Anti-heterologous Ig
Heterologous
anti-GBM
Masugi nephritis.
PMN
Complement
Masugi nephritis
Experimental model of human antiglomerular basement
membrane (anti-GBM) nephritis. The disease is induced by
the injection of rabbit antirat glomerular basement membrane
antibody into rats. The antiserum for passive transfer
is raised in rabbits immunized with rat kidney basement
Low IgG
A
High IgG
A
B
B
C
C
H
H
Mechanism of γ globulin protection from catabolism. IgG (γ) and plasma
prteins (o) (A) are internalized into endosomes of endothelium (B) without
prior binding. In the low pH (H + ) of the endosome (C), binding of IgG is
promoted (D, E, F). IgG retained by receptor recycles to the cell surface
and dissociates in the neutral pH of the extracellular fluid, returning to
circulation (G, H). Unbound proteins are shunted to the lysosomes for
degradation. With “low IgG,” receptor efficiently “rescues” IgG from
catabolism. With “high IgG,” receptor is saturated and excess IgG passes
to catabolism for a net acceleration of IgG catabolism.
D
D
G
G
E
F
E
F
H
H
M