Systemic hypoxia enhances exercise-mediated bactericidal and subsequent apoptotic responses in human neutrophils.
Phagocytosis and oxidative burst are critical host defense mechanisms in which neutrophils clear invading pathogens. Clearing phagocytic neutrophils by triggering apoptosis is an essential process for controlling inflammation. This study elucidates how various exercise bouts with/without hypoxia affected neutrophil bactericidal activity and subsequent apoptosis in humans. Fifteen sedentary males performed six distinct experimental tests in an air-conditioned normobaric hypoxia chamber: two normoxic exercises [strenuous exercise (SE; up to maximal O2 consumption) and moderate exercise (ME; 50% maximal O2 consumption for 30 min) while exposed to 21% O2], two hypoxic exercises (ME for 30 min while exposed to 12% and 15% O2), and two hypoxic exposures (resting for 30 min while exposed to 12% and 15% O2). The results showed that 1) plasma complement-C3a desArg/C4a desArg/C5a concentrations were increased, 2) expressions of L-selectin/lymphocyte functin-associated antigen-1/Mac-1/C5aR on neutrophils were enhanced, 3) phagocytosis of neutrophils to Esherichia coli and release of neutrophil oxidant products by E. coli were elevated, and 4) E. coli-induced phosphotidylserine exposure or caspase-3 activation of neutrophils were promoted immediately and 2 h after both 12% O2 exposure at rest and with ME as well as normoxic SE. Although neither normoxic ME nor breathing 15% O2 at rest influenced these complement- and neutrophil-related immune responses, ME at both 12% and 15% O2 resulted in enhanced complement activation in the blood, expressions of opsonic/complement receptors on neutrophils, or the bactericidal activity and apoptosis of neutrophils. Moreover, the increased neutrophil oxidant production and apoptosis by normoxic SE and hypoxic ME were ameliorated by treating neutrophils with diphenylene iodonium (a NADPH oxidase inhibitor). Therefore, we conclude that ME at 12-15% O2 enhances bactericidal capacity and facilitates the subsequent apoptosis of neutrophils.
Wang
Jong-Shyan
JS
Graduate Institute of Rehabilitation Science, Chang Gung Univ., 259 Wen-Hwa 1st Rd., Kwei-Shan, Tao-Yuan 333, Taiwan. s5492@mail.cgu.edu.tw
Chiu
Ya-Ting
YT
D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001770:Blood Bactericidal Activity / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D015926:Complement C3a / Q000378:metabolism; D015934:Complement C4a / Q000378:metabolism; D015937:Complement C5a, des-Arginine / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000472:pathogenicity*; D015444:Exercise; D006801:Humans; D000860:Hypoxia / Q000276:immunology / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D019041:L-Selectin / Q000097:blood; D016169:Lymphocyte Function-Associated Antigen-1 / Q000097:blood; D016177:Macrophage-1 Antigen / Q000097:blood; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D009861:Onium Compounds / Q000494:pharmacology; D010101:Oxygen Consumption; D010587:Phagocytosis / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000097:blood; D016897:Respiratory Burst / Q000187:drug effects; D013997:Time Factors; D055815:Young Adult
D015415:Biomarkers; C488033:C5AR1 protein, human; D015937:Complement C5a, des-Arginine; D004791:Enzyme Inhibitors; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D009861:Onium Compounds; D010718:Phosphatidylserines; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; C051066:complement C4a, des-Arg; D019041:L-Selectin; C007517:diphenyleneiodonium; D015926:Complement C3a; D015934:Complement C4a; D019255:NADPH Oxidases; C505407:CASP3 protein, human; D053148:Caspase 3