Thermosensitivity of red blood cells from Down's syndrome individuals

Biochemical disturbances of the reactive oxygen species metabolism revealed in subjects with Down's syndrome (DS), and the findings indicating that he at-induced cell alterations have been, at least, partly mediated by reactiv e oxygen species, made the elucidation of the response of trisomic cells to elevated temperatures of special interest. Kinetic analysis of cell-surviv al curves, accompanied by the flow cytometry and the scanning electron micr oscopy (SEM) examinations, and their relationship with the cell membrane fl uidity, were undertaken. At each temperature (48-54 degreesC), D-q paramete rs, representing the ability to accumulate sublethal damages, were similar for both cell groups. D-0 parameters (inverse leakage rates; D-0 = l/k) wer e greater for DS cells at each temperature below 54 degreesC. The haemolysi s sensitivity ratio (HSR) showed that DS erythrocytes were, in average, 1.6 0 times more resistant to heat injury than those from normal subjects. Acti vation energies of haemolysis, calculated according to the Arrhenius equati on, were similar both for normal (290.8 +/- 6.5 [kJ/mol]) and DS erythrocyt es (288.0 +/- 5.5 [kJ/mol]). Flow cytometry studies showed that the scatter ing properties of intact DS erythrocytes (reflecting size, volume, shape an d cell membrane surface morphology) were different than those of normal cel ls. Scanning electron micrographs and scattering diagrams obtained for cell s submitted to heat stress (51 degreesC) confirmed that DS erythrocytes wer e more resistant, to a certain extent, to heat-induced disruption than norm al cells. The steady-state fluorescence anisotropy of TMA-DPH(1-(4-trimethy l-ammoniumphenyl)-6-phenyl-1,3,5-hexatriene)showed that untreated DS erythr ocytes had substantially lower fluidity (r = 0.356 +/- 0.008) of the outer monolayer of cell membranes as compared to normal cells (r = 0.324 +/- 0.01 1). The increase of the cell membrane fluidity during exposure to heat was observed. The greatest elevation of cell membrane fluidity occurred during the preleakage period, immediately upon the heat treatment and was consider ed as a rate-limiting step of heat-induced haemolysis. (C) 2000 Elsevier Sc ience S.A. All rights reserved.