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American Journal of Pathology, Vol 105, 270-278, Copyright © 1981 by American Society for Investigative Pathology

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Giant dense bodies in fibroblasts cultured from beige mice with the Chediak-Higashi syndrome

RA Vincent Jr and SS Spicer

Fibroblasts cultured from the skin of beige mice manifesting the Chediak-Higashi syndrome (CHS), unlike cells derived from normal black mice, exhibited giant dense bodies in the cytoplasm. These megabodies were membrane-delimited and exhibited dense content by electron microscopy, with myelin figures, highly osmiophilic, thick membranous contours, and lucent areas. The megabodies evidenced acid phosphatase ultrastructurally. Cells of both normal and CHS mice contained smaller dense bodies. During a 2--6 hour exposure to colloidal gold, the smaller dense bodies of normal and CHS fibroblasts selectively incorporated the gold spherules and, accordingly, were identified as secondary lysosomes of heterophagic origin. With longer exposure to colloidal gold, the small dense bodies of the normal and CHS cells disclosed increased content of colloidal gold. After 24 hour exposure to colloidal gold, many giant dense bodies also exhibited gold particles, evidencing uptake of endocytosed material into the giant structures and the heterophagic origin of at least some of the content of the bodies. The gold spherules initially incorporated into the giant dense bodies were concentrated in foci along their periphery and indicated fusion of small dense bodies into the giant structures. Transformed normal and CHS cells appeared to contain more abundant myelin figures than nontransformed cells, and these were larger in transformed CHS cells and constituted a major component of their giant dense bodies. The giant inclusions of the transformed CHS cells generally contained little colloidal gold, suggesting their derivation principally through cellular autophagy.