1/5. Improvement of Chediak-Higashi leukocyte function by cyclic guanosine monophosphate.The addition of cholinergic agents and cyclic 3'5'-guanosine monophosphate (cGMP) to polymorphonuclear leukocytes in vitro from a patient with chediak-higashi syndrome corrected the impaired release of the lysosomal enzyme, beta-glucuronidase, to normal. Coinciding with the improvement in degranulation, the bactericidal capacity was enhanced to normal. Similar concentrations of cholinergic agents potentiated chemotaxis to control values. On the other hand, the phagocytic rate of lipopolysaccharide-coated paraffin-oil droplets was not altered by the cholinergic agents. The improvement in chediak-higashi syndrome polymorphonuclear leukocyte function by the addition of cholinergic agents and dibutyryl cGMP suggested disturbed intracellular cyclic nucleotide levels.- - - - - - - - - - ranking = 1keywords = lysosomal enzyme, enzyme (Clic here for more details about this article) |
2/5. Biochemical studies on the leukocytes in chediak-higashi syndrome.blood leukocytes from a patient with chediak-higashi syndrome (CHS) were compared with normal cells for their capacity of extruding (exocytosis) the lysosomal enzyme myeloperoxidase during phagocytosis or after a treatment with the ionophore A23187 and Ca2 . A decreased rate and extent of exocytosis in phagocytizing CHS cells was observed also with the Ca2 ionophore. This suggests that a defect in Ca2 mobilization is not responsible for the impaired secretion of granule content. Isolated granules of CHS cells and of leukocytes were treated with the detergent Triton X-100. Since the solubilization of myeloperoxidase from the CHS granules was much lower than from the normal ones, we suggest that the former organelles have a more resistant membrane.- - - - - - - - - - ranking = 1keywords = lysosomal enzyme, enzyme (Clic here for more details about this article) |
3/5. chediak-higashi syndrome: abnormal lysosomal enzyme levels in granulocytes of patients and family members.Nine lysosomal enzyme activities were examined in granulocytes and lymphocytes from two unrelated patients with chediak-higashi syndrome (CHS) in "accelerated phase" and from their family members. In CHS granulocytes, there was a marked reduction of alpha-mannosidase (E.C. 3.2.1.24), alpha-galactosidase (E.C. 3.2.1.22), and alpha-fucosidase (E.C. 3.2.1.51) activities, which were below 21, 24, and 43% of mean control values, respectively. In CHS lymphocytes, beta-glucuronidase (E.C. 3.2.1.31) and alpha-mannosidase activities were also decreased. In granulocytes of family members, the activities of acid phosphatase (E.C. 3.1.3.2), N-acetyl-beta-glucosaminidase (E.C. 3.2.1.30), aryl sulphatase (E.C. 3.1.6.1), and beta-glucuronidase were significantly higher than the control values (P < 0.001), which were 262, 218, 414, and 180% of mean control values. Neither the inhibitor in CHS granulocytes nor the activator in the heterozygous granulocytes to those enzymes could be found by mixing experiments with normal ones.- - - - - - - - - - ranking = 5.0000834522634keywords = lysosomal enzyme, enzyme (Clic here for more details about this article) |
4/5. Specific protease deficiency in polymorphonuclear leukocytes of chediak-higashi syndrome and beige mice.Peripheral blood leukocytes of three patients with chediak-higashi syndrome (CHS) contained very low or undetectable levels of elastase, the major neutral protease in these cells. Likewise, peritoneal exudate leukocytes of beige mice (the murine counterpart of CHS) contained correspondingly reduced levels of their major neutral protease, a serine enzyme of mol wt 27,000. The elastase deficiency in CHS polymorphonuclear leukocytes might account in part for the high incidence of infections in these patients.- - - - - - - - - - ranking = 8.3452263429396E-5keywords = enzyme (Clic here for more details about this article) |
5/5. On the analysis of the pathophysiology of chediak-higashi syndrome. Defects expressed by cultured melanocytes.BACKGROUND: The chediak-higashi syndrome (CHS) is a disorder that affects the synthesis and/or maintenance of storage/secretory granules in various types of cells. lysosomes of leukocytes and fibroblasts, dense bodies of platelets, azurophilic granules of neutrophils and melanosomes of melanocytes are generally larger in size and irregular in morphology, indicating that a common pathway in storage organellogenesis is affected in patients with CHS. EXPERIMENTAL DESIGN: A pure line of melanocytes has been established using a 2 cm2 shave biopsy from a child with CHS. This 4-week-old male patient had oculocutaneous albinism and expressed neutropenia, impaired platelet function, and no natural killer cell activity. The cultured CHS melanocytes were analyzed for cell biological and biochemical aberrancies. RESULTS: Cultured melanocytes demonstrated some large and/or complexed melanosomes that resembled those observed in melanocytes from ultrastructural sections of the biopsy. Cytoplasmic localization of tyrosinase, tyrosinase-related protein-1 and granulophysin (a 40 kilodalton membrane protein originally identified as a component in dense bodies of platelets) demonstrated a prominent perinuclear accumulation. The basal synthesis of melanin and the activity levels of tyrosine hydroxylase, dihydroxyphenylalanine (DOPA) oxidase, or DOPAchrome tautomerase were comparable to control Caucasian melanocytes in culture. However, melanin synthesis as well as the catalytic activities of tyrosinase were not dramatically upregulated in CHS melanocytes by the addition of isobutyl methylxanthine and cholera toxin in the growth medium when parameters were assayed in cell lysates. In contrast, when assays were performed using live cells, tyrosine hydroxylase demonstrated dramatic upregulation. Medium conditioned by CHS melanocytes demonstrated phenylthiourea-inhibitable tyrosinase activity. Melanocyte lysates and conditioned medium analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and DOPA staining showed an extra, approximately 100 kilodalton soluble protein band with DOPA positivity and tyrosinase immunoreactivity. In addition to tyrosinase, one of three lysosomal enzymes assayed (beta-glucuronidase) was aberrantly secreted into the medium. CONCLUSIONS: These results demonstrate that melanocytes cultured from CHS express a defect in the structure and/or function of the melanosome and abnormal trafficking of some cellular proteins.- - - - - - - - - - ranking = 1keywords = lysosomal enzyme, enzyme (Clic here for more details about this article) |