Impaired Microtubule Assembly and Polymorphonuclear Leucocyte Function in the Chediak‐Higashi Syndrome Correctable by Ascorbic Acid

Summary. It was previously shown that the abnormal surface characteristics and defective bactericidal function of polymorphonuclear leucocytes (PMN) in the Chediak‐Higashi syndrome (CHS) are correlated with impaired microtubule assembly, and in one patient direct electron microscopic evidence for an anomaly in microtubule assembly following surface membrane activation by concanavalin A (Con A). We show here that very few microtubules are visible in CHS leucocytes from two additional patients under conditions where normal PMNs contain abundant microtubules, and that both in vivo and in vitro exposure of the CHS leucocytes to ascorbic acid promotes the assembly of microtubules. This agent, which normalizes chemotaxis and degranulation in CHS leucocytes, is shown also to correct granulocyte adherence in these leucocytes. It is suggested that the improved clinical course of patients with CHS following treatment with ascorbic acid is related at least in part to improvement of microtubule assembly and PMN function by the ascorbic acid.

[1]  L. Boxer,et al.  Enhancement of chemotactic response and microtubule assembly in human leukocytes by ascorbic acid , 1979, Journal of cellular physiology.

[2]  J. Oliver,et al.  Microtubule dynamics and glutathione metabolism in phagocytizing human polymorphonuclear leukocytes , 1978, The Journal of cell biology.

[3]  P. Greengard,et al.  Effects of colchicine on cyclic AMP levels in human leukocytes. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[4]  J. Oliver,et al.  Effects of glutathione-oxidizing agents on microtubule assembly and microtubule-dependent surface properties of human neutrophils , 1976, The Journal of cell biology.

[5]  J. Allen,et al.  Correction of leukocyte function in Chediak-Higashi syndrome by ascorbate. , 1976, The New England journal of medicine.

[6]  Oliver Jm.  Impaired microtubule function correctable by cyclic GMP and cholinergic agonists in the Chediak-Higashi syndrome. , 1976 .

[7]  Oliver Jm.  Concanavalin A cap formation on human polymorphonuclear leukocytes induced by R17934, a new antitumor drug that interferes with microtubule assembly. , 1976 .

[8]  J. Oliver,et al.  Correction of characteristic abnormalities of microtubule function and granule morphology in Chediak-Higashi syndrome with cholinergic agonists. , 1976, The Journal of clinical investigation.

[9]  G. Weissmann,et al.  Concanavalin A induces microtubule assembly and specific granule discharge in human polymorphonuclear leukocytes , 1976, The Journal of cell biology.

[10]  Powell Hc,et al.  Neutrophilic leukocyte inclusions in colchicine intoxication. , 1976 .

[11]  B. Trump,et al.  Autophagocytosis: in vitro induction by microtuble poisons. , 1975, Experimental cell research.

[12]  J. Oliver,et al.  Concanavalin A cap formation on polymorphonuclear leukocytes of normal and beige (Chediak-Higashi) mice , 1975, Nature.

[13]  R. Macgregor,et al.  Inhibition of granulocyte adherence by ethanol, prednisone, and aspirin, measured with an assay system. , 1974, The New England journal of medicine.

[14]  L. Rydgren,et al.  The difference between random movement and chemotaxis. Effects of antitubulins on neutrophil granulocyte locomotion. , 1974, Experimental cell research.

[15]  J. S. Giansanti,et al.  The Chediak-Higashi syndrome. Report of a case and review of the literature. , 1974, Oral surgery, oral medicine, and oral pathology.

[16]  G. Weissmann,et al.  Mechanisms of lysosomal enzyme release from human leukocytes: microtubule assembly and membrane fusion induced by a component of complement. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[17]  G. Weissmann,et al.  MECHANISMS OF LYSOSOMAL ENZYME RELEASE FROM HUMAN LEUKOCYTES , 1973, The Journal of cell biology.

[18]  S. Wolff,et al.  The Chediak-Higashi syndrome: studies in four patients and a review of the literature. , 1972, Medicine.

[19]  R. Root,et al.  Abnormal bactericidal, metabolic, and lysosomal functions of Chediak-Higashi Syndrome leukocytes. , 1972, The Journal of clinical investigation.

[20]  S. Wolff,et al.  The Chediak-Higashi syndrome: studies of host defenses. , 1972, Annals of internal medicine.

[21]  J. Allen,et al.  Improvement of Chediak-Higashi leukocyte function by cyclic guanosine monophosphate. , 1977, Blood.

[22]  J. Oliver.  Concanavalin A cap formation on human polymorphonuclear leukocytes induced by R17934, a new antitumor drug that interferes with microtubule assembly. , 1976, Journal of the Reticuloendothelial Society.

[23]  P. Wolf,et al.  Neutrophilic leukocyte inclusions in colchicine intoxication. , 1976, Archives of pathology & laboratory medicine.

[24]  G. Weissmann,et al.  Mechanisms of lysosomal enzyme release from human leukocytes. II. Effects of cAMP and cGMP, autonomic agonists, and agents which affect microtubule function. , 1974, The Journal of clinical investigation.