calcimycin and Cystinosis

Upon in vitro stimulation with 10 microM ionophore A 23187 for 5 min at 37 degrees C, the generation of leukotriene (LT) C4 in polymorphonuclear leukocytes (PMNL) from nine untreated cystinotic children was significantly increased compared with that in eight control children (p < 0.01) and 25 normal adults (p < 0.001) (417.4 +/- 70.0 versus 177.0 +/- 30.9 and 164.9 +/- 19.5 pmol/l x 10(7) cells, respectively). Concomitantly with the increased generation of LTC4, LTB4 production in PMNL from untreated cystinotic children was decreased compared with controls, whereas the total amount of LTA4 derivatives was similar in the three groups. The increase in LTC4 production was not related to the number of eosinophils present in the PMNL preparations from cystinotic children, which was similar to that of control subjects. PMNL from cystinotic children treated with cysteamine, an aminothiol compound that decreases the intracellular cystine content, generated smaller amounts of LTC4 upon ionophore A 23187 stimulation than PMNL from untreated cystinotic children. In addition, abrogation of the cysteamine treatment for 3 or 4 d led to an increase in LTC4 production. These findings suggest that the metabolic abnormalities taking place in infantile cystinosis may favor the biosynthesis of LTC4 from PMNL.

Topics: Adult; Calcimycin; Child; Child, Preschool; Cystine; Cystinosis; Eosinophils; Heterozygote; Humans; Leukotriene C4; Neutrophils; Stimulation, Chemical