ALTERED LEUKOTRIENE GENERATION IN LEUKOCYTES FROM CYSTINOTIC CHILDREN

Upon in vitro stimulation with 10 mu M ionophore A 23187 for 5 min at 37 degrees C, the generation of leukotriene (LT) C-4 in polymorphonucl ear leukocytes (PMNL) from nine untreated cystinotic children was sign ificantly 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/1 x 10(7) cells, respectively). Concomi tantly with the increased generation of LTC(4), LTB(4), production in PMNL from untreated cystinotic children was decreased compared with co ntrols, whereas the total amount of LTA(4) derivatives was similar in the three groups. The increase in LTC(4) production was not related to the number of eosinophils present in the PMNL preparations from cysti notic children, which was similar to that of control subjects. PMNL fr om cystinotic children treated with cysteamine, an aminothiol compound that decreases the intracellular cystine content, generated smaller a mounts of LTC, upon ionophore A 23187 stimulation than PMNL from untre ated cystinotic children. In addition, abrogation of the cysteamine tr eatment for 3 or 4 d led to an increase in LTC(4) production. These fi ndings suggest that the metabolic abnormalities taking place in infant ile cystinosis may favor the biosynthesis of LTC, from PMNL.