Cooperation of chloroquine and blood platelets in inhibition of polymorphonuclear leukocyte chemiluminescence.
Effect of activated blood platelets and chloroquine on concentration of reactive oxygen species produced by polymorphonuclear leukocytes (PMNL) stimulated with Ca(2+)-ionophore A23187 was investigated. Oxygen metabolites localized outside PMNL were visualized by isoluminol enhanced chemiluminescence, whereas chemiluminescence, enhanced with luminol and measured in the presence of the extracellular scavengers superoxide dismutase and catalase, was used for the detection of radicals originated intracellularly. Significant reduction of chemiluminescence was observed in the presence of platelets (added to PMNL in the physiological cell ratio 50:1) and of chloroquine (10 and 100 micromol/L). Although chloroquine decreased effectively both the extra- as well as the intracellular part of the chemiluminescence signal, the activity of platelets occurred largely outside PMNL. Serotonin liberated from platelets by A23187 appeared to be involved in inhibition of chemiluminescence; its concentrations achieved in platelet supernatants were found to be sufficient for elimination of PMNL-derived oxygen metabolites. The presented results indicated that chloroquine and blood platelets cooperate in inhibition of chemiluminescence because their common effect was found to be much more extensive than reduction induced by these inhibitors separately. Therefore, for accurate prediction of drug effect in the whole organism, the use of multicellular test systems seems to be pertinent.
Jancinová
V
V
Institute of Experimental Pharmacology, Slovak Academy of Sciences and Institute of Haematology and Transfusiology, Bratislava, Slovak Republic. exfavega@savba.sk
Nosál
R
R
Drábiková
K
K
Danihelováa
E
E
D001792:Blood Platelets / Q000502:physiology*; D002738:Chloroquine / Q000494:pharmacology*; D006801:Humans; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000032:analysis; D012701:Serotonin / Q000378:metabolism
D017382:Reactive Oxygen Species; D012701:Serotonin; D002738:Chloroquine