scholarly journals Red Blood Cells: Tethering, Vesiculation, and Disease in Micro-Vascular Flow

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 971
Author(s):  
Robert J. Asaro ◽  
Pedro Cabrales

The red blood cell has become implicated in the progression of a range of diseases; mechanisms by which red cells are involved appear to include the transport of inflammatory species via red cell-derived vesicles. We review this role of RBCs in diseases such as diabetes mellitus, sickle cell anemia, polycythemia vera, central retinal vein occlusion, Gaucher disease, atherosclerosis, and myeloproliferative neoplasms. We propose a possibly unifying, and novel, paradigm for the inducement of RBC vesiculation during vascular flow of red cells adhered to the vascular endothelium as well as to the red pulp of the spleen. Indeed, we review the evidence for this hypothesis that links physiological conditions favoring both vesiculation and enhanced RBC adhesion and demonstrate the veracity of this hypothesis by way of a specific example occurring in splenic flow which we argue has various renderings in a wide range of vascular flows, in particular microvascular flows. We provide a mechanistic basis for membrane loss and the formation of lysed red blood cells in the spleen that may mediate their turnover. Our detailed explanation for this example also makes clear what features of red cell deformability are involved in the vesiculation process and hence require quantification and a new form of quantitative indexing.

1993 ◽  
Vol 174 (1) ◽  
pp. 109-122
Author(s):  
G B Nash ◽  
S Egginton

We have studied the comparative rheology of individual red blood cells from humans and rainbow trout (Oncorhynchus mykiss) at their natural body temperatures. Trout red blood cells were large ellipsoids (about 16 microns x 11.5 microns x 2.5 microns) with a mean volume of 250 fl, a surface area of approximately 350 microns 2 and an elongated nucleus of about 9 microns x 5 microns. Although much larger than human red cells (diameter 8 microns, V = 92 fl, A = 136 microns 2), both theoretical calculation and experimental aspiration into micropipettes indicated that the limiting size of a cylindrical vessel that both types of cell could enter was approximately 3 microns. Nevertheless, individual trout red cells had much longer transit times through 5 microns filter pores and were much slower to enter 3-4 microns diameter micropipettes. Interestingly, the relative deformability of the trout cells depended on the pore size and applied pressure, with entry times for trout and human cells converging as pipette diameter increased. The relatively poor overall cellular deformability of the trout cells reflected their membrane rigidity (shear elastic modulus 4-5 times higher than that of human membrane), as well as their large size and the presence of a prominent nucleus. Capillary diameters in trout muscle are similar to those in the human microcirculation (about 3 microns), while systemic driving pressures are much lower. Therefore, either red cell deformability is a less critical circulatory parameter than has previously been thought, or the apparently disadvantageous blood rheology of trout is adequate because of the lower demand for tissue perfusion.


1972 ◽  
Vol 53 (3) ◽  
pp. 809-818 ◽  
Author(s):  
P. S. Vassar ◽  
J. M. Hards ◽  
D. E. Brooks ◽  
B. Hagenberger ◽  
G. V. F. Seaman

The effects of formaldehyde, acetaldehyde, and glutaraldehyde on human red blood cells were investigated. It was found that (a) The surface negative charge of the erythrocytes at pH 7 was increased 10% by glutaraldehyde, but not by the other two aldehydes. (b) The effect of incomplete fixation of the red blood cells was demonstrated by hemoglobin leakage studies The leakage of hemoglobin subsequent to formaldehyde treatment was especially pronounced Acetaldehyde-fixed cells showed some leakage of hemoglobin after an hour of exposure to the fixative, whereas glutaraldehyde-fixed cells showed no hemoglobin leakage. (c) All three aldehydes caused K+ leakage during fixation. The concentrations of K+ in the fixing solutions all reached the same level, but whereas the leakage with glutaraldehyde was immediate, that with formaldehyde was more gradual and that with acetaldehyde reached a steady state only after 24 hr. (d) The effects of the aldehydes on red cell deformability and swelling revealed that glutaraldehyde hardened the cells within 15 min, formaldehyde within 5 hr, while acetaldehyde required at least 24 hr to produce appreciable fixation. (e) The hematocrit changes accompanying the fixation process depended upon cell volume changes and loss of deformability.


Blood ◽  
1959 ◽  
Vol 14 (4) ◽  
pp. 399-408 ◽  
Author(s):  
WILLIAM H. CROSBY

Abstract During all the stages of a red cell’s life the normal spleen exerts a normal function. Eight of these functions have been considered: (1) erythropoiesis; (2) an effect upon red cell production; (3) an effect upon maturation of the red cell surface; (4) the reservoir function; (5) the "culling function"; (6) iron turnover and storage; (7) the "pitting function"; (8) destruction of old red cells.


1989 ◽  
Vol 203 ◽  
pp. 381-400 ◽  
Author(s):  
D. Halpern ◽  
T. W. Secomb

An analysis is presented of the mechanics of red blood cells flowing in very narrow tubes. Mammalian red cells are highly flexible, but their deformations satisfy two significant constraints. They must deform at constant volume, because the contents of the cell are incompressible, and also at nearly constant surface area, because the red cell membrane strongly resists dilation. Consequently, there exists a minimal tube diameter below which passage of intact cells is not possible. A cell in a tube with this diameter has its critical shape: a cylinder with hemispherical ends. Here, flow of red cells in tubes with near-minimal diameters is analysed using lubrication theory. When the tube diameter is slightly larger than the minimal value, the cell shape is close to its shape in the critical case. However, the rear end of the cell becomes flattened and then concave with a relatively small further increase in the diameter. The changes in cell shape and the resulting rheological parameters are analysed using matched asymptotic expansions for the high-velocity limit and using numerical solutions. Predictions of rheological parameters are also obtained using the assumption that the cell is effectively rigid with its critical shape, yielding very similar results. A rapid decrease in the apparent viscosity of red cell suspensions with increasing tube diameter is predicted over the range of diameters considered. The red cell velocity is found to exceed the mean bulk velocity by an amount that increases with increasing tube diameter.


2021 ◽  
Vol 12 ◽  
Author(s):  
Perumal Thiagarajan ◽  
Charles J. Parker ◽  
Josef T. Prchal

Normal human red blood cells have an average life span of about 120 days in the circulation after which they are engulfed by macrophages. This is an extremely efficient process as macrophages phagocytose about 5 million erythrocytes every second without any significant release of hemoglobin in the circulation. Despite large number of investigations, the precise molecular mechanism by which macrophages recognize senescent red blood cells for clearance remains elusive. Red cells undergo several physicochemical changes as they age in the circulation. Several of these changes have been proposed as a recognition tag for macrophages. Most prevalent hypotheses for red cell clearance mechanism(s) are expression of neoantigens on red cell surface, exposure phosphatidylserine and decreased deformability. While there is some correlation between these changes with aging their causal role for red cell clearance has not been established. Despite plethora of investigations, we still have incomplete understanding of the molecular details of red cell clearance. In this review, we have reviewed the recent data on clearance of senescent red cells. We anticipate recent progresses in in vivo red cell labeling and the explosion of modern proteomic techniques will, in near future, facilitate our understanding of red cell senescence and their destruction.


Blood ◽  
1988 ◽  
Vol 72 (6) ◽  
pp. 2056-2059
Author(s):  
WM Lande ◽  
DL Andrews ◽  
MR Clark ◽  
NV Braham ◽  
DM Black ◽  
...  

To determine whether the vasoocclusive severity of homozygous sickle cell (SS) disease is influenced by cellular dehydration, we correlated the incidence of painful crisis with steady-state measurements of red cell hydration. Sixteen children with SS disease were followed for 3.3 to 8 years (mean, 6.8 years), and a single crisis rate was calculated for each patient. At the time of well visits, cellular hydration was assessed by measuring cell deformability, the percentage of red cells with a density greater than or equal to 1.1056 g/mL, and the percentage of irreversibly sickled cells (ISC). The incidence of painful crisis showed a strong positive correlation with Omax, a deformability measurement reflecting cellular hydration (r = .84, P less than .002), and with hemoglobin concentration (r = .59, P = .04). That is, higher crisis rates were observed in patients with less dehydrated, more deformable red cells and also in patients with higher hemoglobin concentrations. Furthermore, cell deformability and hemoglobin concentration were independent predictors of the incidence of painful crisis, which is consistent with separate effects of these two red cells parameters on vasoocclusive severity.


Blood ◽  
1961 ◽  
Vol 18 (3) ◽  
pp. 349-363 ◽  
Author(s):  
STANLEY YACHNIN ◽  
FRANK H. GARDNER

Abstract Agglutinins for various artificially altered red blood cells belong to the class of 19S macroglobulins, which migrate electrophoretically as fast gamma or slow beta globulins. The agglutinin activity of serum for altered red cells is readily destroyed by sulfhydryl compounds. Hemolysins for altered red cells are not readily recoverable from serum fractions prepared by starch block electrophoresis or density gradient ultracentrifugation, but, when present, are found to have the same properties. This information lends credence to the concept of these serum factors as examples of "natural antibody," although the stimulus to their formation is not understood. The sera from patients with various types of hemolytic anemias and various dysproteinemias including macroglobulinemia were found to contain normal amounts of altered red cell agglutinins and hemolysins. The sera from three patients with congenital agammaglobulinemia were studied. Two of these sera contained agglutinins and hemolysins for altered red blood cells, as well as isohemolysins and isoagglutinins. The significance of this finding is discussed. The "T" agglutinin and the agglutinin for periodate-treated red cells, both of which are macroglobulins, have been shown by other workers to be absent from newborn sera. Their inability to cross the placenta can be explained by their large size.


Blood ◽  
1983 ◽  
Vol 62 (1) ◽  
pp. 214-217 ◽  
Author(s):  
PA Aarts ◽  
PA Bolhuis ◽  
KS Sakariassen ◽  
RM Heethaar ◽  
JJ Sixma

Abstract The hematocrit is one of the main factors influencing platelet adherence to the vessel wall. Raising the hematocrit causes an increase of platelet accumulation of about an order of magnitude. Our studies concern the role of red cell size. We have studied this effect using an annular perfusion chamber, according to Baumgartner, with human umbilical arteries and a steady-flow system. Normal human red blood cells (MCV 95 cu mu) increased platelet adherence sevenfold, as the hematocrit increases from 0 to 0.6. Small erythrocytes from goats (MCV 25 cu mu) caused no increment in adherence in the same hematocrit range. Rabbit erythrocytes (MCV 70 cu mu) caused an intermediate increase in adherence. Red blood cells from newborns (MCV 110–130 cu mu) caused a larger increase in platelet adherence than normal red cells at hematocrit 0.4. These results were further confirmed with large red blood cells from two patients. Experiments with small red cells (MCV 70 cu mu) of patients with iron deficiency showed that platelet adherence was similar to normal red cells, provided the red cell diameter was normal. Small red blood cells of a patient with sideroblastic anemia caused decreased adherence. These data indicate that red cell size is of major importance for platelet adherence. Red cell diameter is more important than average volume. However, for size differences in the human range, the hematocrit remains the dominant parameter.


2000 ◽  
Vol 89 (3) ◽  
pp. 1198-1204 ◽  
Author(s):  
Robert L. Conhaim ◽  
Lance A. Rodenkirch ◽  
Kal E. Watson ◽  
Bruce A. Harms

High lung inflation pressures compress alveolar septal capillaries, impede red cell transit, and interfere with oxygenation. However, recently introduced acellular hemoglobin solutions may enter compressed lung capillaries more easily than red blood cells. To test this hypothesis, we perfused isolated rat lungs with fluorescently labeled diaspirin cross-linked hemoglobin (DCLHb; 10%) and/ or autologous red cells (hematocrit, 20). Septal capillaries were compressed by setting lung inflation pressure above vascular pressures (zone 1). Examination by confocal microscopy showed that DCLHb was distributed throughout alveolar septa. Furthermore, this distribution was not affected by adding red blood cells to the perfusate. We estimated the maximum acellular hemoglobin mass within septa to be equivalent to that of 15 red blood cells. By comparison, we found an average of 2.7 ± 4.6 red cells per septum in zone 1. These values increased to 30.4 ± 25.8 and 50.4 ± 22.1 cells per septum in zones 2 and 3, respectively. We conclude that perfusion in zone 1 with a 10% acellular hemoglobin solution may increase the hemoglobin concentration per septum up to fivefold compared with red cell perfusion.


1981 ◽  
Author(s):  
G M Housley ◽  
G V R Born

Earlier observations of ours have suggested that, under in vitro conditions resembling those under which platelets function haemostatically in vivo, their activation is promoted by the red cells. Seme of the evidence suggested that this is through limited haemolysis with release of ADP. However, newly determined time relationships make this uncertain. Could red cells provide ADP without haemolysis?Crtheir flow properties affect the process more? To analyse the problem, we are determining dependence of red cell deformability on membrane constitution; and release of haemoglobin and adeninenucleotides under different conditions. Ten percent human red cell suspensions in physiological salines flow under constant pressures through 2, 3, 4 and 5 pm micropore filters, the flow rate measured continuously with an electronic balance. Initial flow rates are increased by fluidising agents, eg. ethanol, and decreased by agents with opposite effect. Our results are consistent with the new hypothesis of S.J. Singer on the mode of action of amphipathic agents, such as chlorpromazine, on red cell membranes.


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