Chediak-Higashi Syndrome: Variable Cytochemical Reactivity of Giant Inclusions in Polymorphonuclear Leukocytes

Abstract

Neutrophils from the peripheral blood of patients with the Chediak-Higashi syndrome (CHS) contain large numbers of giant granules. Previous studies have demonstrated that the huge neutrophil organelles contain hydrolytic enzymes and are, therefore, massive lysosomes. The basis for the inability of giant granules to react with phagocytic vacuoles containing foreign particulates taken up by CHS neutrophils has not been determined. In the present investigation we have examined the ultrastructural cytochemistry of the huge inclusions in neutrophils from 3 patients. Electron-dense reaction product of the acid phosphatase reaction stained the giant inclusions and a few normal-sized azurophilic granules in the process of fusion with them. The amount of reaction product deposited in the huge organelles and its distribution, however, were extremely variable, even in the same cell. Myeloperoxidase staining revealed a similar variability in the intensity and distribution of its electrondense reaction product. The findings suggest that giant primary granules in circulating CHS neutrophils retain characteristics similar to newly formed azurophilic lysosomes in promyelocytes and myelocytes. Dilution of enzyme reaction products and variability in their localization indicate that most of the giant primary granules undergo transformation or incorporation into huge secondary lysosomes, which are virtually unable to participate in the degranulation reaction after uptake of foreign particulates by CHS neutrophils.

Key Words:

• Chediak-Higashi syndrome
• polymorphonuclear leukocytes
• giant granules
• electron cytochemistry