K Sahashi1, T Ibi, G Zhang. 1. Fourth Department of Medicine, Aichi Medical University.
Abstract
UNLABELLED: In the advanced stage of dystrophinopathy, cardiac dysfunction is a serious complication for prognosis. Recently, an angiotensin converting enzyme (ACE), which converts angiotensin (A) 1 to A 2, has been reported to be effective for cardiac insufficiency. The A 2 is produced more dominantly in the path via the production of a neutral serine protease, chymase (MW 25,000), secreted from the mast cell. We have observed localization of chymase in diseased human skeletal muscle tissues, and evaluated its clinical significance. The frozen muscle biopsied specimens from 91 neuromuscular disorders (muscular dystrophies, inflammatory myopathies and neurogenic muscular disorders) were stained by using monoclonal antibody against the chymase, and the positive cells in a whole sectional field were counted. In the serial sections, we also performed routine histochemistry and immunostainings of immunological markers (CD4, CD8 and others) as well as the apoptotic proteins for comparison. RESULTS: The chymase-positive mast cells were scattered mainly in the endomysium, partly in the perimysium and around small vessels. Although the positivity was not disease specific, more numerous strongly positive cells were observed in dystrophinopathy and inflammatory myopathies, but less in myotonic dystrophy and neurogenic muscle disorders. In the normal control muscle, however, strongly positive cells appeared less frequently than in the above mentioned diseased muscles. The chymase-positive cells partly corresponded to the ubiquitin-positive ones, but perforin, granzyme A, Fas and Bcl-2 did not. In conclusion, the chymase-positive mast cell may play a primary or secondary role in the diseased muscle, and their more abundant appearance in dystrophinopathy and some other myopathies suggest the effectiveness of an ACE blocker, an anti-chymase drug.
UNLABELLED: In the advanced stage of dystrophinopathy, cardiac dysfunction is a serious complication for prognosis. Recently, an angiotensin converting enzyme (ACE), which converts angiotensin (A) 1 to A 2, has been reported to be effective for cardiac insufficiency. The A 2 is produced more dominantly in the path via the production of a neutral serine protease, chymase (MW 25,000), secreted from the mast cell. We have observed localization of chymase in diseased human skeletal muscle tissues, and evaluated its clinical significance. The frozen muscle biopsied specimens from 91 neuromuscular disorders (muscular dystrophies, inflammatory myopathies and neurogenic muscular disorders) were stained by using monoclonal antibody against the chymase, and the positive cells in a whole sectional field were counted. In the serial sections, we also performed routine histochemistry and immunostainings of immunological markers (CD4, CD8 and others) as well as the apoptotic proteins for comparison. RESULTS: The chymase-positive mast cells were scattered mainly in the endomysium, partly in the perimysium and around small vessels. Although the positivity was not disease specific, more numerous strongly positive cells were observed in dystrophinopathy and inflammatory myopathies, but less in myotonic dystrophy and neurogenic muscle disorders. In the normal control muscle, however, strongly positive cells appeared less frequently than in the above mentioned diseased muscles. The chymase-positive cells partly corresponded to the ubiquitin-positive ones, but perforin, granzyme A, Fas and Bcl-2 did not. In conclusion, the chymase-positive mast cell may play a primary or secondary role in the diseased muscle, and their more abundant appearance in dystrophinopathy and some other myopathies suggest the effectiveness of an ACE blocker, an anti-chymase drug.