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. 1978 Sep;92(3):745–753.

The Chédiak-Higashi syndrome. Evidence that defective leukotaxis is primarily due to an impediment by giant granules.

C C Clawson, J G White, J E Repine
PMCID: PMC2018262  PMID: 686156

Abstract

The primary defect of the Chédiak-Higashi syndrome (CHS) which links the several known neutrophil abnormalities in this disorder remains enigmatic. In an attempt to clarify the mechanism of one of the abnormalities of CHS neutrophils, ie, chemotactic migration, the effect of filter pore size was examined in the standard Boyden chamber assay. The response of normal neutrophils to a gradient of zymosan-activated serum was not influenced by increasing the filter pore size from 5 to 8 microgram. However, while CHS neutrophils showed a significant reduction in migratory response from the controls with 5-mu filters, the difference was eliminated when 8-mu filters were employed. Again, when an arachidonic acid gradient was used as the stimulus, migration of CHS neutrophils through 8-mu filters equalled that of controls. These findings indicate the intact nature of the surface receptor and motility systems of the CHS neutrophils and further suggest that the previously defined chemotactic defect in these cells can be explained in terms of the mechanical impediment provided by the CHS giant cytoplasmic granules.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blume R. S., Bennett J. M., Yankee R. A., Wolff S. M. Defective granulocyte regulation in the Chediak-Higashi syndrome. N Engl J Med. 1968 Nov 7;279(19):1009–1015. doi: 10.1056/NEJM196811072791901. [DOI] [PubMed] [Google Scholar]
  2. Boxer L. A., Rister M., Allen J. M., Baehner R. L. Improvement of Chediak-Higashi leukocyte function by cyclic guanosine monophosphate. Blood. 1977 Jan;49(1):9–17. [PubMed] [Google Scholar]
  3. Boxer L. A., Watanabe A. M., Rister M., Besch H. R., Jr, Allen J., Baehner R. L. Correction of leukocyte function in Chediak-Higashi syndrome by ascorbate. N Engl J Med. 1976 Nov 4;295(19):1041–1045. doi: 10.1056/NEJM197611042951904. [DOI] [PubMed] [Google Scholar]
  4. Clark R. A., Kimball H. R. Defective granulocyte chemotaxis in the Chediak-Higashi syndrome. J Clin Invest. 1971 Dec;50(12):2645–2652. doi: 10.1172/JCI106765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clark R. A., Kimball H. R., Padgett G. A. Granulocyte chemotaxis in the Chediak-Higashi syndrome of mink. Blood. 1972 May;39(5):644–649. [PubMed] [Google Scholar]
  6. Dent P. B., Fish L. A., White L. G., Good R. A. Chediak-Higashi syndrome. Observations on the nature of the associated malignancy. Lab Invest. 1966 Oct;15(10):1634–1642. [PubMed] [Google Scholar]
  7. Gallin J. I., Bujak J. S., Patten E., Wolff S. M. Granulocyte function in the Chediak-Higashi syndrome of mice. Blood. 1974 Feb;43(2):201–206. [PubMed] [Google Scholar]
  8. Gallin J. I., Klimerman J. A., Padgett G. A., Wolff S. M. Defective mononuclear leukocyte chemotaxis in the Chediak-Higashi syndrome of humans, mink, and cattle. Blood. 1975 Jun;45(6):863–870. [PubMed] [Google Scholar]
  9. Goetzl E. J., Wasserman S. I., Gigli I., Austen K. F. Enhancement of random migration and chemotactic response of human leukocytes by ascorbic acid. J Clin Invest. 1974 Mar;53(3):813–818. doi: 10.1172/JCI107620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Oliver J. M. Impaired microtubule function correctable by cyclic GMP and cholinergic agonists in the Chediak-Higashi syndrome. Am J Pathol. 1976 Nov;85(2):395–418. [PMC free article] [PubMed] [Google Scholar]
  11. Oliver J. M., Zurier R. B. Correction of characteristic abnormalities of microtubule function and granule morphology in Chediak-Higashi syndrome with cholinergic agonists. J Clin Invest. 1976 May;57(5):1239–1247. doi: 10.1172/JCI108392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Padgett G. A. Neutrophilic function in animals with the Chediak-Higashi syndrome. Blood. 1967 Jun;29(6):906–915. [PubMed] [Google Scholar]
  13. Root R. K., Rosenthal A. S., Balestra D. J. Abnormal bactericidal, metabolic, and lysosomal functions of Chediak-Higashi Syndrome leukocytes. J Clin Invest. 1972 Mar;51(3):649–665. doi: 10.1172/JCI106854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Stossel T. P., Root R. K., Vaughan M. Phagocytosis in chronic granulomatous disease and the Chediak-Higashi syndrome. N Engl J Med. 1972 Jan 20;286(3):120–123. doi: 10.1056/NEJM197201202860302. [DOI] [PubMed] [Google Scholar]
  15. White J. G. Giant organelles containing tubules in Chediak-Higashi lymphocytes. Am J Pathol. 1972 Nov;69(2):225–238. [PMC free article] [PubMed] [Google Scholar]
  16. White J. G. The Chediak-Higashi syndrome: a possible lysosomal disease. Blood. 1966 Aug;28(2):143–156. [PubMed] [Google Scholar]
  17. Wolff S. M. The Chediak-Higashi syndrome: studies of host defenses. Ann Intern Med. 1972 Feb;76(2):293–306. doi: 10.7326/0003-4819-76-2-293. [DOI] [PubMed] [Google Scholar]

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