Hypoxia impairs metabolic functions by decreasing activity and expression of ATP-consuming processes. To separate hypoxia from systemic effects, we tested whether hypoxia at high altitude affects basal and PMA-stimulated leukocyte metabolism and how this compares to acute (15 min) and 24 h of in vitro hypoxia. Leukocytes were prepared at low altitude and ∼24 h after arrival at 4559 m. Mitochondrial oxygen consumption (JO2) was measured by respirometry, oxygen radicals by electron spin resonance spectroscopy, both at a Po2= 100 mmHg (JO2,100) and 20 mmHg (JO2,20). Acute hypoxia of leukocytes decreased JO2at low altitude. Exposure to high altitude decreased JO2,100, whereas JO2,20was not affected. Acute hypoxia of low-altitude samples decreased the activity of complexes I, II, and III. At high altitude, activity of complexes I and III were decreased when measured in normoxia. Stimulation of leukocytes with PMA increased JO2,100at low (twofold) and high altitude (five-fold). At both locations, PMA-stimulated JO2was decreased by acute hypoxia. Basal and PMA-stimulated reactive oxygen species (ROS) production were unchanged at high altitude. Separate in vitro experiments performed at low altitude show that ∼75% of PMA-induced increase in JO2was due to increased extra-mitochondrial JO2(JO2,res; in the presence of rotenone and antimycin A). JO2,reswas doubled by PMA. Acute hypoxia decreased basal JO2,resby ∼70% and PMA-stimulated JO2,resby about 50% in cells cultured in normoxia and hypoxia (1.5% O2; 24 h). Conversely, 24 h in vitro hypoxia decreased mitochondrial JO2,100and JO2,20, extra-mitochondrial, basal, and PMA-stimulated JO2were not affected. These results show that 24 h of high altitude but not 24 h in vitro hypoxia decreased basal leukocyte metabolism, whereas PMA-induced JO2and ROS formation were not affected, indicating that prolonged high-altitude hypoxia impairs mitochondrial metabolism but does not impair respiratory burst. In contrast, acute hypoxia impairs respiratory burst at either altitude.
Bactrian camels (Camelus bactrianus) has physio-biochemical adaptation to high altitude
