The Chediak-Higashi Syndrome: Cytoplasmic Sequestration in Circulating Leukocytes

In the course of investigations into the nature of the giant granulation anomaly of leukocytes from patients with the Chediak-Higashi syndrome, an unusual process was observed in white cells from three patients with the disease. Small, normal-sized, lysosomal granules present in abundance in C.H. leukocytes were observed in the concentric arrangements around areas of cytoplasm. Apparent union of the small granules resulted in development of "doughnut-shaped" channels of fused granular material. Serial sections have indicated that the organelles formed in this manner are complete spheres or discs. Cytoplasmic constituents enclosed by the double-walled vacuoles were frequently observed in various stages of destruction. Ultrastructural cytochemical staining for acid phosphatase defined the presence of this lysosomal enzyme in the matrix between the unit membranes of the double-walled vacuoles, and associated with fragments of enclosed cytoplasm undergoing digestion. Sequestration and destruction of areas of C.H. cell cytoplasm within membrane-bound vacuoles is strikingly similar to the process of autophagy reported in other tissues. The possible relationship of the process of cytoplasmic sequestration to the giant lysosomes which characterize the leukocytes of patients with the C.H. syndrome is discussed.