Introduction: When polycythemic high altitude adapted persons descend to sea level, a fast reduction of red blood cell (RBC) mass occurs as an adaptive response to the normoxic environment. The RBC mass regulation is carried out by a decrease in erythropoietin (EPO) synthesis and a concomitant selective lysis of young erythrocytes (neocytes), which is called neocytolysis. The cellular and molecular mechanisms underlying this selective RBC destruction are still matter of debate. Previous investigations (Trial J. et al., 2001) have suggested that a decrease in EPO level could be associated to changes in interactions between splenic endothelial cells, macrophages and RBC, triggering lysis of neocytes. To gain some information on the phenotypical features leading young RBC to engulfment and destruction by macrophages, we studied a group of four mountain climbers (2 male and 2 female, age 30-45 years), whose RBC were analysed before and after a Himalaya mountaineering expedition implying 47 days of staying at altitudes ranging from 1300 m (Kathmandu) to 8150 m (Dhaulagiri summit). In particular we studied those membrane markers which are supposed to prevent or to favour RBC destruction. Material and Methods: Blood samples (20 ml) were drawn from each subject before and 7 days after high altitude dwelling. The following haematological parameters were investigated: RBC count (cells/ìL), Hematocrit (Ht, %), Haemoglobin concentration [Hb, g/dL]. Classical Wintrobe`s parameters were then calculated: Mean Corpuscular Volume (MCV, fL), Mean Corpuscular Haemoglobin Concentration (MCHC, %), Mean Corpuscular Haemoglobin Content (MCH, pg). The Red Cell Distribution Width (RDW) was also obtained by means of an automatic counter. Moreover the following serum concentrations were determined: Transferrin, Iron, Ferritin and EPO. We separated the RBC`s age-based subsets (young, middle aged and old), by centrifugation on Percoll® density gradient (Omodeo-Sale et al., 2003) of the blood samples obtained before and after high altitude dwelling. Subsequently, we made a comparative study of the above mentioned RBC`s subsets by analysing the following parameters: 1) cell counts of each subset, 2) ATP content of the RBC and 3) expression of some membrane markers, i.e.: CD47, CD55, CD58, CD59, phosphatydilserine (PS), (Test et al., 1991; Davies et al., 1993; van Engeland et al., 1998; Bonomini et al.; 1999, Oldenborg et al, 2000). Results and Discussion: Preliminary results have not shown remarkable differences between clinical standard haematological parameters before and after high altitude exposure. However, comparisons of EPO serum levels and RBC counts, determined on blood samples, drawn before and 7 days after the high altitude exposure, were suggestive of an ongoing neocytolytic process. Indeed, we observed a significant reduction of young and middle aged RBC counts, which were reduced to the 3% and to the 1.3% (mean values) of the corresponding RBC`s subsets evaluated before the high altitude exposure. These quantitative changes were associated with decreased levels of expression, albeit not significant, of the membrane markers CD55, CD58, CD59, which are known to prevent RBC`s lysis. Furthermore, on the outer surface of the young and middle aged RBC`s membranes an increase in phosphatydilserine (PS) was observed in two subjects. PS is believed to be an "apoptotic" marker promoting RBC`s phagocytosis by the reticulo endothelial system macrophages. Conclusions: Taken together the above preliminary data indicate that phenotypical changes in young RBC could contribute to their recognition by phagocytes and, therefore, to their destruction giving rise to the neocytolysis upon reentry to sea level after high altitude exposure. However, neocytolysis does not seem to be limited to the young RBC`s population, but it involves also middle aged RBCs.
© Copyright 2005 International Congress Mountain & Sport. Updating study and research from laboratory to field. 11th-12th November 2005. Rovereto (TN) - Italy. Programme and book of abstracts. Veröffentlicht von Centro Interuniversitario di Ricerca in Bioingegneria e Scienze Motorie. Alle Rechte vorbehalten.