Alterations in sensitivity to calcium and enzymatic hydrolysis of membranes from sickle cell disease and trait erythrocytes

Abstract

Normally, human erythrocytes display several responses to elevated intracellular calcium levels. These include a shape transition from discocyte to spherocyte, shedding of microvesicles into the extracellular fluid, and enhanced susceptibility to the hydrolytic action of secretory phospholipase A 2 . These responses to elevated intracellular calcium were all blunted in erythrocytes containing hemoglobin S. The reduction of both the shape transition and the shedding of microvesicles were greater than the impairment of phospholipase susceptibility, and both correlated strongly with the intracellular content of hemoglobin S. In contrast to the response to elevated intracellular calcium, erythrocytes containing hemoglobin S displayed a 2.5-fold increase in basal susceptibility to phospholipase A 2 compared to control erythrocytes in the absence of ionophore. The effect was more prominent among samples from patients heterozygous for hemoglobin S than in samples from homozygous individuals. These results reveal additional abnormalities in the membranes of sickle cell erythrocytes beyond those described previously and demonstrate that red blood cells from both heterozygous and homozygous are affected. Furthermore, they suggest a possible means by which sickle cell disease and trait patients may display enhanced vulnerability to inflammatory stimuli. Am. J. Hematol. 72:162-169, 2003.

Mechanisms Governing the Level of Susceptibility of Erythrocyte Membranes to Secretory Phospholipase A2

“…Normally, cell membranes resist hydrolysis by the enzyme (Smith et al, 2001;Wilson et al, 1999;Nielson et al, 2000). However, under certain conditions, such as during apoptosis or after cellular trauma, they become highly susceptible (Smith et al, 2001;Wilson et al, 1999;Judd et al, 2003;Nielson et al, 2000;Atsumi et al, 1997). We have used human erythrocytes as a model to study the factors governing membrane susceptibility to sPLA 2 (Vest et al, 2004;Smith et al, 2001;Harris et al, 2001;Best et al, 2002).…”

Divalent Cations Increase Lipid Order in Erythrocytes and Susceptibility to Secretory Phospholipase A2

“…Not all cell membranes are susceptible to hydrolysis by sPLA 2 . Healthy cells resist attack by the enzyme; however, phospholipids in apoptotic and diseased or damaged cells are vulnerable (Atsumi et al, 1997;Judd et al, 2003;Nielson et al, 2000;Wilson et al, 1999). Apparently, this increased level of hydrolysis is a consequence of differences in membrane physical properties between healthy and damaged cells (Smith et al, 2001;Wilson et al, 1999).…”

First case of immune‐mediated haemolytic anaemia associated to imatinib mesylate

“…Recently, Judd et al. (12) described alterations in sensitivity to calcium and enzymatic hydrolysis of membranes from sickle‐cell disease and trait erythrocytes that revealed additional abnormalities beyond those previously described. They also showed that red blood cells from both heterozygous and homozygous are affected, suggesting a possible means by which sickle‐cell trait patients may display enhanced vulnerability to inflammatory stimuli.…”