CHEDIAK-HIGASHI-SYNDROME - NATURE OF THE GIANT NEUTROPHIL GRANULES AND THEIR INTERACTIONS WITH CYTOPLASM AND FOREIGN PARTICULATES .1. PROGRESSIVE ENLARGEMENT OF THE MASSIVE INCLUSIONS IN MATURE NEUTROPHILS .2. MANIFESTATIONS OF CYTOPLASMIC INJURY AND SEQUESTRATION .3. INTERACTIONS BETWEEN GIANT ORGANELLES AND FOREIGN PARTICULATES

  • 1 January 1980
    • journal article
    • research article
    • Vol. 98  (1) , 151-+
Abstract
Defective bactericidal functioning of polymorphonuclear leukocytes (PMN) from patients with the Chediak-Higashi syndrome (CHS) was related to a failure of the giant granules characteristic of the disorder to participate in degranulation after uptake of foreign particulates by neutrophils. The reason massive CHS inclusions do not fuse with and discharge their contents into phagocytic vacuoles was not defined. The huge organelles in CHS neutrophils may originate by fusion of small azurophilic granules in promyelocytes and myelocytes. Present investigations into the cytopathology of the CHS employed EM and ultrastructural cytochemistry to characterize the progressive enlargement of the huge bodies in mature PMN, their interaction with cytoplasmic constituents resulting in various manifestations of cell injury and their response to foreign particulates. Each study clarifies abnormal features of the giant organelles essential to the understanding of their role in the defective bactericidal function of CHS neutrophils. Most of the huge inclusions in PMN are not primary lysosomes. The interaction and fusion of giant azurophilic granules with each other, with normal-sized primary and secondary granules and with cytoplasmic components converts the massive primary granules into huge secondary lysosomes. Transformation to secondary lysosomes represents a critical alteration in the state of the giant granules that underlies their damaging influence on the cytoplasm and loss of reactivity with phagocytic vacuoles.