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Evidence implicating calpain (Ca 2+ ‐dependent neutral protease) in the destructive thrombocytopenia of the Wiskott‐Aldrich syndrome
Author(s) -
Kenney D. M.,
Reid R.,
Parent D. W.,
Rosen F. S.,
RemoldO'Donnell E.
Publication year - 1994
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1994.tb06737.x
Subject(s) - calpain , platelet , protease , stimulation , immunology , ionophore , chemistry , wiskott–aldrich syndrome , lymphocyte , neutral protease , calcium , microbiology and biotechnology , endocrinology , medicine , biology , biochemistry , enzyme , gene
Summary. The Wiskott‐Aldrich syndrome (WAS) is an inherited platelet/T‐lymphocyte disease characterized by small platelets, thrombocytopenia and immunodeficiency. Because degradative events have a significant role, we directly examined calpain (Ca 2+ ‐dependent neutral protease), a prominent protease in the affected cells, by functional and antigenic quantitation. Calpain activity in platelets of seven WAS patients was decreased to 59 ± 3.7% (P < 0.01) relative to platelets of 11 normals. Platelets of two patients with immune thrombocytopenia had normal calpain activity. By immunoblotting, μ‐procalpain, the μ‐calpain species in resting (unstimulated) blood cells, was decreased in platelets of nine WAS patients to 58 ± 14.6% (P < 0.01) relative to paired normals. In contrast, μ‐procalpain levels in lymphocytes of seven WAS patients did not differ from normal lymphocytes. Normal platelets and lymphocytes have different mechanisms for Ca 2+ ‐dependent μ‐procalpain activation. On addition of ionophore and Ca 2+ to stirred platelets, 80kD μ‐procalpain was rapidly (0.5 min) and quantitatively converted to 76 kD active μ‐calpain; this process was the same in WAS platelets. In lymphocytes, μ‐procalpain activation was slow, only partially complete (40min), and the active species was 78kD. The marked depletion of calpain in WAS platelets demonstrated in this study may result from inappropriate stimulation of platelets and be related to the severe thrombocytopenia that characterizes this disease.