Neutrophil Tolerance to Oxidative Stress Induced by Hypoxia/Reoxygenation ANTONI SUREDA a , JOAN M. BATLE b , PERE TAULER a , NURIA CASES a , ANTONI AGUILO ´ a , JOSEP A. TUR a and ANTONI PONS a, * a Laboratori de Cie `ncies de l’Activitat Fı ´sica, Departament de Biologia Fonamental i Cie `ncies de la Salut, Universitat de les Illes Balears, Campus Universitari, Crtra. Valldemossa, Km 7.5, E-07122-Palma de Mallorca, Illes Balears, Spain; b MEDISUB, C/Alcanada, Alcu ´ dia, Illes Balears, Spain Accepted by Professor J. Vina (Received 27 April 2004; In revised form 28 June 2004) Repetitive episodes of hypoxia/reoxygenation induce cellular adaptations resulting in a tolerance process against oxidative stress. We studied the effects of chronic episodes of hypoxia/reoxygenation on neutrophil anti- oxidant defenses, neutrophil oxidative capability, and oxidative damage induced in neutrophils and plasma. Seven professional apnea divers participated in the study. Blood samples were taken under basal conditions, after a diving apnea session, and under basal conditions after five consecutive days of diving apnea sessions (basal post- diving). Chronic episodes of hypoxia/reoxygenation increased malondialdehyde (MDA), carbonyl derivates and creatine kinase (CPK) in plasma. Neutrophil catalase (CAT) levels were higher in basal post-diving. Neutrophil oxidative burst was maintained after diving, although the maximum response was delayed in basal post-diving. Neutrophil thioredoxin reductase (TR) activity increased in basal post-diving, and glutathione reductase (GR) activity was maintained. Chronic, repetitive episodes of diving apnea induce neutrophil adaptations in order to delay the oxidative burst response and to facilitate protein reduction. Diving apnea could be a good model to study tolerance to the oxidative stress generated by hypoxia/ reoxygenation. Keywords: Oxidative stress; Oxidative tolerance; Antioxidants; Neutrophil; Hypoxia/Reoxygenation; Diving apnea Abbreviations: ALT, alanine transaminase; ANOVA, analysis of variance; APIR, acute phase immune response; AST, aspartate transaminase; CAT, catalase; CL, luminol chemiluminescence; CPK, creatine kinase; DNPH, 2,4-dinitrophenylhydrazine; GGT, glutamil transpeptidase; GR, glutathione reductase; LDH, lactate dehydrogenase; MPO, myeloperoxidase; NO, nitric oxide; OZ, opsonized zymosan; ROS, reactive oxygen species; SOD, superoxide dismutase; TR, thioredoxin reductase INTRODUCTION Circulating neutrophils are important in tissue surveillance, repair and adaptation of human skeletal muscle. Interactions between neutrophils and muscle may play a significant role in modulating the course of muscle injury and repair after oxidative damage. [1] Although activated neutrophils present increased capabilities to syn- thesize reactive oxygen species (ROS) that could produce oxidative damage, [2,3] this increase in oxidative activity could inhibit neutrophil functions by auto-oxidative processes. [4,5] Long-duration or damaging exercise increases oxygen consumption and causes a disturbance between intracellular pro- oxidant and antioxidant homeostasis. [2,3] Several studies have investigated the ROS producing activity of circulating neutrophils after exercise by luminol-dependent chemiluminescence (CL) with controversial results. [6–8] Luminol CL mainly detects the MPO-dependent formation of HOCl. In most cases, the luminol-dependent CL response was augmented after exercise, [8] but repeated exercise sessions could reduce the CL. [9] Exhaustive exercise could inhibit neutrophil response to exogenous stimuli. This impaired neutrophil func- tion may lead to a predisposition to infection after extensive exercise. [10] The role of neutrophils after exercise is not exactly known. ISSN 1071-5762 print/ISSN 1029-2470 online q 2004 Taylor & Francis Ltd DOI: 10.1080/10715760400000984 *Corresponding author. Tel.: þ 34-971173171. Fax: þ 34-971173184. E-mail: dbsapb0@uib.es Free Radical Research, Volume 38 Number 9 (September 2004), pp. 1003–1009