Cystine Accumulation and Clearance by Normal and Cystinotic Leukocytes Exposed to Cystine Dimethyl Ester

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 79; no. 14; pp. 4446 - 4450
• Main Authors: Steinherz, Reuben, Tietze, Frank, Gahl, William A., Triche, Timothy J., Chiang, Hung, Modesti, Andrea, Schulman, Joseph D.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01.07.1982; National Acad Sciences
• Subjects: Amino acids; Chemical suspensions; Cystine - analogs & derivatives; Cystine - metabolism; Cystinosis; Cystinosis - blood; Esters; Fibroblasts; Humans; In Vitro Techniques; Leukocytes; Leukocytes - metabolism; Lysosomes; Lysosomes - metabolism; Neutrophils; Neutrophils - metabolism; Neutrophils - ultrastructure; Radioactive decay; Time Factors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.79.14.4446

Upon exposure to 0.25 mM cystine dimethyl ester, normal and cystinotic leukocytes accumulate substantially more intracellular cystine than is present endogenously in cystinotic cells. Leukocytes loaded by exposure to cystine dimethyl ester may have abnormally lucent and distended lysosomes, and the cystine is compartmentalized within the granular fraction of the cells. After the cells are exposed to cystine dimethyl ester, cystine clearance from normal leukocytes is much faster than from cystinotic cells. The ratios of labeled cysteine-N-ethylmaleimide to cystine are also greater in normals than in cystinotics 60 min after termination of loading. No overlap in ranges of cystine clearance half-times or cysteine-N-ethylmaleimide to cystine ratios was observed in normal compared to cystinotic leukocytes. Limited experiments with fibroblasts exposed to cystine dimethyl ester suggest a correspondingly prolonged cystine clearance for cystinotic cells. These experiments provide evidence for defective clearance of cystine from cystinotic lysosomes in situ.