Correction of leukocyte function in Chediak-Higashi syndrome by ascorbate

• Published in: The New England journal of medicine Vol. 295; no. 19; p. 1041
• Main Authors: Boxer, L A, Watanabe, A M, Rister, M, Besch, Jr, H R, Allen, J, Baehner, R L
• Format: Journal Article
• Language: English
• Published: United States 04.11.1976
• Subjects: Ascorbic Acid - pharmacology; Ascorbic Acid - therapeutic use; Blood Bactericidal Activity - drug effects; Chediak-Higashi Syndrome - drug therapy; Chediak-Higashi Syndrome - enzymology; Chediak-Higashi Syndrome - immunology; Cyclic AMP - blood; Cyclic GMP - blood; Female; Glucuronidase - blood; Humans; In Vitro Techniques; Infant; Leukocytes - enzymology; Leukocytes - immunology; Microtubules - drug effects; Monocytes - drug effects; Stimulation, Chemical
• ISSN: 0028-4793
• DOI: 10.1056/NEJM197611042951904

Because ascorbate potentiates chemotaxis of normal leukocytes, we examined the effect of ascorbate on polymorphonuclear leukocytes from a patient with the Chediak-Higashi syndrome. Chemotactic migration was 104+/-16 leukocytes per 10 fields (mean+/-S.D.) initially and 258+/-44 (P less than 0.001) after ascorbate, as compared to 182+/-10 in controls. There was no bactericidal activity by 40 minutes in the patient's untreated leukocytes. After ascorbate bactericidal activity of patient and untreated control cells was the same. The addition of ascorbate reduced cAMP levels in the patient's cells from a mean of 34.5 pmoles per 10(7) polymorphonuclear leukocytes to 5.9, as compared to a control value of 3.1+/-1.4. The association of elevated cAMP and impaired function in the polymorphonuclear leukocytes of patients with the Chediak-Higashi syndrome may be related to abnormal microtubular assembly.