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Neocytolysis of red blood cells following high altitude exposure
No full textIntroduction: 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
Cytotoxicity and apoptosis mediated by two peptides of innate immunity
No full textAntimicrobial peptides are present in a wide range
of species, from protozoa to man, as effector molecules
of innate immunity. Several bovine precursors of antimicrobial
peptides have recently been identified, as
deduced from cDNA, and assigned to the cathelicidin
family. Two of these are the proforms of the antimicrobial
peptides BMAP-27 and BMAP-28, which share
a similar amino acid sequence, structural conformation,
and toxic activity toward several bacterial and
fungal strains. Here we report that they are cytotoxic
to human tumor cells and normal proliferating, but
not resting, lymphocytes at concentrations comparable
to those microbiocidal. This effect is primarily due
to damage of plasma membrane integrity. A more detailed
investigation of the U937 cell line revealed that
a Ca21 influx into the cytosol occurs in the early steps
of permeabilization. The perturbation of the membrane
structure and the Ca21 influx are followed by
programmed death. A similar apoptosis inducing effect
is also observed on in vitro activated human lymphocytes
Neocytolysis and alterations of erythrocytes over a short term spaceflight
No full textWhen a fast red cell mass reduction is needed, neocytolysis, i.e. destruction of young red blood cells (RBC), occurs. This process takes place in astronauts over the first days space-flight as part of the adaptive response to the microgravity environment. On blood samples drawn from four astronauts before and after a 12-15 days space-flight, we analysed a panel of hematological parameters and some phenotypic features of age-related RBC subsets, which can be linked to a neocytolytic process.
After the space-flight, changes in plasma ferritin levels and in reticulocyte number indicated that a neocytolytic process likely occurred in flight. Furthermore the percentage and the viability of early generated RBC was decreased and on the outer membrane layer a small number of those left over exposed phosphatydilserine (PS), a phospholipid able to trigger macrophage ingestion. A decreased expression of the membrane molecules CD55, which protects red cells from complement mediated lysis and CD47, which inhibits macrophage phagocytosis, was also observed in young erythrocytes. It is likely that the membrane phenotype of early-generated RBC makes them more susceptible to destruction
Analysis of membrane antigens on in vitro activated peripheral blood lymphocytes
No full textPhytohaemagglutinin P (PHA) was used as a polyclonal activator to induce in vitro activation of bovine lymphocytes purified from peripheral blood by isopicnic centrifugation on Ficoll Hipaque gradients. After 3 days of incubation, human recombinant IL-2 was added to the cell cultures, to induce a long term proliferation of the cells. Over the cell culture period (12 days) the expression of membrane molecules was investigated by FACS analysis by using the corresponding monoclonal antibodies recognising the membrane antigens. The following markers were monitored at 2 day intervals: BoCD4, BoCD8, MHC II DR and gamma delta subset. The study was conducted from lymphocytes from 5 steers. It was concluded that upon activation BoCD4, BoCD8 and DR molecules seem to be upregulated. In contrast, a decrease in gamma delta subset was detectable during activation period with PHA and IL- 2
Analysis of membrane antigens on in vitro activated bovine peripheral blood lymphocytes.
No full textMetodiche per evidenziare le immunoglobuline di membrana dei linfociti per mezzo dell'immunofluorescenza
No full textFunctional characterization of an antigen involved in an early step of T-cell activation
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