ENHANCEMENT OF REACTIVE OXYGEN SPECIES FORMATION IN STABLE AND UNSTABLE ASTHMATIC-PATIENTS

There is increasing evidence to suggest that human blood polymorphonuc lear neutrophils (PMNs) and monocytes play an important role in the in flammatory processes of asthma. In asthmatic patients, PMNs and monocy tes were shown to be activated more than in healthy subjects. We inves tigated the capacity of these two cell, populations to generate reacti ve oxygen species (ROS) in stable and unstable asthmatic patients. The two populations of asthmatic patients were identified by asthma activ ity, as expressed by clinical events occurring within 2 weeks prior to the study, Oxygen species formation was analysed for isolated purifie d PMNs and monocytes (Mos) by chemiluminescence (CL) using lucigenin a nd luminol as luminescent probes. CL was determined on nonstimulated a nd on phorbol myristate acetate (PMA)-stimulated cells. The stimulatab ility coefficient (PMA-stimulated/nonstimulated cell ratio) of each ce ll population was then calculated. Resting PMNs and Mos generated sign ificantly greater amounts of ROS in stable asthmatic patients, and muc h more in unstable asthmatic patients, as compared to healthy subjects , both in lucigenin and luminol enhanced CL. Non O-2.(-) ROS productio n from PMA-stimulated PMNs and Mos was identical in unstable asthmatic patients and in healthy subjects, whereas a significant decrease was observed in stable asthmatic patients, as assessed by luminol enhanced CL. PMA-stimulated cells showed no difference in O-2.(-) generation, as assessed by lucigenin enhanced CL. However, the stimulatability coe fficient of all asthmatic patients was always significantly lower than that of healthy subjects. These results suggest that there are differ ences in priming and stimulation of Ros production from PMNs and Mos b etween stable and unstable asthmatic patients. Release of oxygen speci es from these cells may be implicated in the pathophysiology of unstab le asthma.