We used immunofluorescent microscopy to characterize the abnormal granules in neutrophils from five patients with Chediak-Higashi disease. Monospecific antiserums to the azurophilic markers myeloperoxidase, elastase, cathepsin G and lysozyme, and to the specific granule markers lactoferrin and lysozyme, were labeled with fluorescein and rhodamine and were used to demonstrate two antigens in the same cell simultaneously. The abnormal granules in Chediak-Higashi neutrophils contained both azurophilic and specific granule markers. Normalappearing lactoferrin-positive granules were also present, but normal azurophilic granules were not seen. Analysis of bone-marrow samples from two of these patients suggested that the abnormal granules were formed during granulocyte maturation by the progressive aggregation and fusion of normally formed azurophilic and specific granules. These results are consistent with a membrane abnormality or a defect of microtubular function leading to inappropriate granule fusion, and suggest that the granular abnormality is more generalized than previously appreciated. (N Engl J Med 298:693–698, 1978) CHEDIAK-Higashi disease is a rare familial disorder characterized by partial oculocutaneous albinism, photophobia and severe recurrent infections.1 Neutrophils from these patients are deficient in chemotactic2 and bactericidal activities,3 and there is delayed fusion of the abnormal granules with phagocytic vacuoles.34 Oliver and Zurier56 and Boxer et al.78 have shown that microtubular abnormalities may be responsible for these defects and that ascorbic acid therapy may correct certain functional but not morphologic abnormalities of these cells. The pathological hallmark of the disease is the presence of massive intracellular inclusions. Although these structures are most easily demonstrated in leukocytes, they are also present.
ASJC Scopus subject areas