scholarly journals The unique red cell heterogeneity of SC disease: crystal formation, dense reticulocytes, and unusual morphology

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 2104-2112 ◽  
Author(s):  
C Lawrence ◽  
ME Fabry ◽  
RL Nagel

Abstract Knowledge concerning SS (homozygous for the beta s gene) red blood cell (RBC) heterogeneity has been useful for understanding the pathophysiology of sickle cell anemia. No equivalent information exists for RBCs of the compound heterozygote for the beta s and beta c genes (SC) RBCs. These RBCs are known to be denser than most cells in normal blood and even most cells in SS blood (Fabry et al, J Clin Invest 70:1284, 1981). We have analyzed the characteristics of SC RBC heterogeneity and find that: (1) SC cells exhibit unusual morphologic features, particularly the tendency for membrane “folding” (multifolded, unifolded, and triangular shapes are all common); (2) SC RBCs containing crystals and some containing round hemoglobin (Hb) aggregates (billiard-ball cells) are detectable in circulating SC blood; (3) in contrast to normal reticulocytes, which are found mainly in a low-density RBC fraction, SC reticulocytes are found in the densest SC RBC fraction; and (4) both deoxygenation and replacement of extracellular Cl- by NO3- (both inhibitors of K:Cl cotransport) led to moderate depopulation of the dense fraction and a dramatic shift of the reticulocytes to lower density fractions. We conclude that the RBC heterogeneity of SC disease is very different from that of SS disease. The major contributions of properties introduced by HbC are “folded” RBCs, intracellular crystal formation in circulating SC cells, and apparently a very active K:Cl cotransporter that leads to unusually dense reticulocytes.

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 2104-2112
Author(s):  
C Lawrence ◽  
ME Fabry ◽  
RL Nagel

Knowledge concerning SS (homozygous for the beta s gene) red blood cell (RBC) heterogeneity has been useful for understanding the pathophysiology of sickle cell anemia. No equivalent information exists for RBCs of the compound heterozygote for the beta s and beta c genes (SC) RBCs. These RBCs are known to be denser than most cells in normal blood and even most cells in SS blood (Fabry et al, J Clin Invest 70:1284, 1981). We have analyzed the characteristics of SC RBC heterogeneity and find that: (1) SC cells exhibit unusual morphologic features, particularly the tendency for membrane “folding” (multifolded, unifolded, and triangular shapes are all common); (2) SC RBCs containing crystals and some containing round hemoglobin (Hb) aggregates (billiard-ball cells) are detectable in circulating SC blood; (3) in contrast to normal reticulocytes, which are found mainly in a low-density RBC fraction, SC reticulocytes are found in the densest SC RBC fraction; and (4) both deoxygenation and replacement of extracellular Cl- by NO3- (both inhibitors of K:Cl cotransport) led to moderate depopulation of the dense fraction and a dramatic shift of the reticulocytes to lower density fractions. We conclude that the RBC heterogeneity of SC disease is very different from that of SS disease. The major contributions of properties introduced by HbC are “folded” RBCs, intracellular crystal formation in circulating SC cells, and apparently a very active K:Cl cotransporter that leads to unusually dense reticulocytes.


Blood ◽  
1982 ◽  
Vol 60 (6) ◽  
pp. 1332-1336 ◽  
Author(s):  
MG Luthra ◽  
DA Sears

Abstract To determine whether diminished activity of the Ca++ extrusion pump could account for the high levels of red blood cell (RBC) Ca++ in sickle cell anemia (SS), we measured calmodulin-sensitive Ca++ ATPase activity in normal and SS RBC. Hemolysates prepared with saponin were compared, since such preparations expressed maximum ATPase activities, exceeding isolated membranes or reconstituted systems of membranes plus cytosol, SS RBC hemolysates had greater Ca++ ATPase activity than normal hemolysates; they exhibited higher Mg++ and Na+ + K+ ATPase activities as well. Assays on density (age) fractions of SS and normal red cells demonstrated that all ATPase activities were highest in low density (young) cells, and activities in SS red cells exceeded those in normals in all fractions studied. Thus, when studied under conditions that maximize enzyme activity, Ca++ ATPase activity, like Mg++ and Na+ + K+ ATPase, is actually increased in SS RBC, probably due to the young red cell population present. The elevated Ca++ levels in these cells are more likely due to an increased Ca++ leak or abnormal calcium binding than to defective extrusion by the ATPase pump.


Blood ◽  
1982 ◽  
Vol 60 (6) ◽  
pp. 1332-1336
Author(s):  
MG Luthra ◽  
DA Sears

To determine whether diminished activity of the Ca++ extrusion pump could account for the high levels of red blood cell (RBC) Ca++ in sickle cell anemia (SS), we measured calmodulin-sensitive Ca++ ATPase activity in normal and SS RBC. Hemolysates prepared with saponin were compared, since such preparations expressed maximum ATPase activities, exceeding isolated membranes or reconstituted systems of membranes plus cytosol, SS RBC hemolysates had greater Ca++ ATPase activity than normal hemolysates; they exhibited higher Mg++ and Na+ + K+ ATPase activities as well. Assays on density (age) fractions of SS and normal red cells demonstrated that all ATPase activities were highest in low density (young) cells, and activities in SS red cells exceeded those in normals in all fractions studied. Thus, when studied under conditions that maximize enzyme activity, Ca++ ATPase activity, like Mg++ and Na+ + K+ ATPase, is actually increased in SS RBC, probably due to the young red cell population present. The elevated Ca++ levels in these cells are more likely due to an increased Ca++ leak or abnormal calcium binding than to defective extrusion by the ATPase pump.


1984 ◽  
Vol 51 (02) ◽  
pp. 186-188 ◽  
Author(s):  
A Szczeklik ◽  
R J Gryglewski ◽  
K Sladek ◽  
E Kostka-Trąbka ◽  
A Żmuda

SummaryDihomo-γ-linolenic acid (DHLA), a precursor of monoenoic anti-aggregatory prostaglandins (PGE1, PGD2), was administered for 4 weeks in a daily dose of 1.0 g into 33 patients with atherosclerosis on a basis of a double-blind trial. Comparison of treatment and placebo groups revealed elevation of DHLA in red cell lipids in DHLA-treated subjects. No differences, however, between the two groups could be observed in platelet aggregability, thromboxane A2 generation by platelets, serum cholesterol, PGE1 and PGE2 levels, and in inhibitory activity of low-density lipoproteins against prostacyclin synthetizing system in arteries. The dietary supplementation used did not lead to distinct antithrombotic effects.


1970 ◽  
Vol 175 (1039) ◽  
pp. 183-200 ◽  

Karyotyping and blood grouping methods were used to identify sheep twin chimaeras. Evidence that an exchange of blood cell precursors (the origin of chimaerism) had taken place in utero was obtained by examining lymphocytes in culture and finding the chromosomes of both sexes in one individual, or by finding admixture of red cell antigens, haemoglobin or ‘X ’ protein. Where chimaerism of sex chromosomes was found the pairs had identical red cell types, but two separate populations of red cells were not always identifiable. The four females in the pairs studied were freemartins. No correlation was found between the relative proportions of the two red cell populations and those of the two white cell populations. In one pair of chimaeric ewes, breeding tests showed that the major red cell populations in each case were the true genetic type. In the freemartins no correlation was found between the degree of masculinity and the numbers of male lymphocytes. A possible correlation of masculinity with red cell proportions is discussed.


Vox Sanguinis ◽  
1999 ◽  
Vol 77 (2) ◽  
pp. 97-102 ◽  
Author(s):  
J. Wildt-Eggen ◽  
J.G. Schrijver ◽  
P.A. Kuiper-Kramer ◽  
M. Bins ◽  
H.C. Prooijen

1996 ◽  
Vol 13 (01) ◽  
pp. 27-33 ◽  
Author(s):  
Steven Inglis ◽  
Andrzej Lysikiewicz ◽  
Amy Sonnenblick ◽  
Jane Streltzoff ◽  
James Bussel ◽  
...  

2012 ◽  
Vol 303 (9) ◽  
pp. R959-R967 ◽  
Author(s):  
Daniel W. Nuno ◽  
Sarah K. England ◽  
Kathryn G. Lamping

Vascular smooth muscle contraction occurs following an initial response to an increase in intracellular calcium concentration and a sustained response following increases in the sensitivity of contractile proteins to calcium (calcium sensitization). This latter process is regulated by the rhoA/rho kinase pathway and activated by serotonin. In multiple cell types, signaling molecules compartmentalize within caveolae to regulate their activation. We hypothesized that serotonin differentially compartmentalizes rhoA within caveolar versus noncaveolar lipid rafts to regulate sustained vascular contractions. To test this hypothesis, we measured aortic contractions in response to serotonin in wild-type (WT) and cav-1-deficient mice (cav-1 KO). RhoA-dependent contractions in response to serotonin were markedly augmented in arteries from cav-1 KO mice despite a modest reduction in rhoA expression compared with WT. We found that under basal conditions, rhoA in WT arteries was primarily localized within high-density sucrose gradient fractions but temporally shifted to low-density fractions in response to serotonin. In contrast, rhoA in cav-1 KO arteries was primarily in low-density fractions and shifted to high-density fractions in a similar timeframe as that seen in WT mice. We conclude that localization of rhoA to caveolar versus noncaveolar lipid rafts differentially regulates its activation and contractions to rhoA-dependent agonists with greater activation associated with its localization to noncaveolar rafts. Disruption of rhoA localization within caveolae may contribute to increased activation and enhanced vascular contractions in cardiovascular disease.


2003 ◽  
Vol 94 (1) ◽  
pp. 38-42 ◽  
Author(s):  
R. D. Telford ◽  
G. J. Sly ◽  
A. G. Hahn ◽  
R. B. Cunningham ◽  
C. Bryant ◽  
...  

There is a wide body of literature reporting red cell hemolysis as occurring after various forms of exercise. Whereas the trauma associated with footstrike is thought to be the major cause of hemolysis after running, its significance compared with hemolysis that results from other circulatory stresses on the red blood cell has not been thoroughly addressed. To investigate the significance of footstrike, we measured the degree of hemolysis after 1 h of running. To control for the potential effects of oxidative and circulatory stresses on the red blood cell, the same subjects cycled for 1 h at equivalent oxygen uptake. Our subjects were 10 male triathletes, who each completed two separate 1-h sessions of running and cycling at 75% peak oxygen uptake, which were performed in random order 1 wk apart. Plasma free hemoglobin and serum haptoglobin concentrations were measured as indicators of hemolysis. We also measured methemoglobin as a percentage of total hemoglobin immediately postexercise as an indicator of red cell oxidative stress. Plasma free hemoglobin increased after both running ( P < 0.01) and cycling ( P < 0.01), but the increase was fourfold greater after running ( P < 0.01). This was reflected by a significant fall in haptoglobin 1 h after the running trials, whereas no significant changes occurred after cycling at any sample point. Methemoglobin increased twofold after both running and cycling ( P < 0.01), with no significant differences between modes of exercise. The present data indicate that, whereas general circulatory trauma to the red blood cells associated with 1 h of exercise at 75% maximal oxygen uptake may result in some exercise-induced hemolysis, footstrike is the major contributor to hemolysis during running.


2015 ◽  
Vol 39 (2) ◽  
pp. 26-31
Author(s):  
Alia Hussein Ali

     The aim of this study is to explain the effect of Ethanolic extract 70% of Metracaria chamomella on some physiological parameters in male rabbits. Twelve adult male rabbits were used in this study and were divided equally into two groups: First group was control (C) and received normal saline for four weeks, the second group (Treated group) was intubated orally with ethanolic extract of Metracaria chamomella in a dose 70 mg/kg B.W. for four weeks. Blood samples were collected by heart puncture from each animal at the end of experiment. Blood sample was divided into a part for hematological study and a part for biochemical analysis. The value of serum urea, and creatinine were reduced in animals that received Metracaria chamomella extract at dose of 70 mg/ kg B.W. as compared with the control group. Significant decrease in serum activity of aspartate aminotransferase alanine aminotransferase and alkaline phosphatase activity was observed in Metracaria treated animal as compared with the control group. This study explained that there was significant increase in serum total protein, serum albumin and serum globulin in treated animals as compared with the control group. The value of total cholesterol, serum triacylglycerol, serum low density lipoprotein cholesterol and very low density lipoprotein cholesterol concentration were reduced significantly in animal received Metracaria chamomella extract while the high density lipoprotein cholesterol was elevated significantly as compared with control group. While the effect of Metracaria chamomella extract on blood picture showed no changes in red blood cell count, hemoglobin concentration and hematocrit value but showed significant decrease in platelet count, and significant   increase in white blood cell count as compared with control group. Over all this study explained that Metracaria chamomella extract had Reno protective and hypolipidimic effect in male rabbit.  


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