Neocytolysis of red blood cells following high altitude exposure

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 following questions: 1) Do 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? But 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 (8)? Methods: A �� � –4� .�T� A group of four mountain climbers was studied (age 28–4 3 years, two males and two females). Their hematological 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 (14) that are partially lost by RBCs during in vitro and in vivo aging (15) were measured. The expression of CD47 (14) and phosphatidylserine (PS) exposure on the outer membrane were also measured. Results: Upon return to sea level, analysis showed a shift to a “senescent-like” phenotype in all RBCs subpopulations, EPO concentration was lower in all subjects as compared with the values measured in control blood samples. Afterthe 6-day descent 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. Conclusions: The changes make the red cells function more effective even at low PO2 targeting possibly the neocytes to phagocytosis once the mountain climbers return to sea level, i.e. to normoxia. Beside the membrane changes the presence of fetal haemoglobin could imbalance the oxygen uptake/delivery by RBCs in normoxia making them more susceptible to oxidative stress and, ultimately, directing them to “senescence” and phagocytosis.