NEOCYTOLYSIS OF RED BLOOD CELLS FOLLOWING HIGH ALTITUDE EXPOSURE

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NEOCYTOLYSIS OF RED BLOOD CELLS FOLLOWING HIGH ALTITUDE EXPOSURE

Journal Title: Medicina Sportiva - Year 2012, Vol 16, Issue 2

Abstract

Introduction: The cellular changes, driven by hypoxia exposure, represent an adequate response to the high altitude environment making newly generated RBCs more fit to manage oxygen uptake and delivery.Objective: To answer the following questions: 1) Are these changes still advantageous upon return to normoxia? 2) Does HIF mediated EPO’s increase, in high altitude give rise to a plethora of scarcely selected, hypoxia adapted neocytes whose phenotype makes them susceptible to phagocytosis, upon return to normoxia?3) Does EPO’s decrease, occurring during de-acclimatisation, the main cause triggering neocytolysis, as the abrogation of neocytolysis in vivo by EPO administration seems to suggest? Methods: A first group of 4 mountain climbers was studied (age 28–43 years, 2 males and 2 females). Their hemato¬logical parameters and RBC phenotype were analysed before and after 53 days acclimatization at high altitude (≥ 4500 m). The RBCs populations were fractionated by density separation into age-based subsets (young, middle-aged and old), the RBCs counts of the three age classes were assessed and some phenotypical features of RBCs from these subsets were investigated by flow cytometry. In particular, the expression of CD55 and CD59 that are partially lost by RBCs during in vitro and in vivo aging were measured. The expression of CD47 and phosphatidylserine (PS) exposure on the outer membrane were also measured. In a second group of five mountain climbers (age 41-53 years, 4 male, 1 female,) possible changes in the expression of fetal haemoglobin was analysed by flow cytometry, western blotting and quantitative RT-PCR performed on reticulocytes and neocytes generated at high altitude (17 days at 3100 -5600 m a.s.l.).Results: Upon return to sea level a dramatic decrease in the number of RBCs in the low and middle density subsets and a corresponding increase of cells in the dense subset was observed. Moreover, the analyses showed a shift to a “senescent-like” phenotype in all RBCs subpopulations as shown by the decrease of expression of CD55, CD59 and CD47 and by increased exposure of PS. EPO concentration was lower in all subjects as compared with the values measured in control blood samples. In the second group of mountain climbers, a slight but significant Increase In fetal he¬moglobin expression by neocytes generated at high altitude was observed (from 1% to 12% of circulating RBCs).

Authors and Affiliations

Guglielmo Antonutto, Angela Risso

Keywords

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EP ID EP74183
DOI 10.5604/17342260.1001883
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