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

Abstract

Abnormal surface characteristics and defective bactericidal function of polymorphonuclear leukocytes (PMN) in the Chediak-Higashi syndrome (CHS) were previously correlated with impaired microtubule assembly, and in 1 patient with direct EM evidence for an anomaly in microtubule assembly following surface membrane activation by concanavalin (Con) A. Very few microtubules were visible in CHS leukocytes from 2 additional patients under conditions where normal PMN contain abundant microtubules, and in vivo as well as in vitro exposure of the CHS leukocytes to ascorbic acid promoted the assembly of microtubules. This agent, which normalized chemotaxis and degranulation in CHS leukocytes, corrected granulocyte adherence in these leukocytes. The improved clinical course of patients with CHS following treatment with ascorbic acid is at least partly related to improvement of microtubule assembly and PMN function by the ascorbic acid.