Blood flow in the capillary bed

From arteries to veins, the blood has to go through the ‘capillary’ blood vessels. These blood vessels are so small that often their diameter is smaller than that of the red blood cells. Intimate interactions occur, therefore, between the blood cells and the blood vessels.

A general survey of recent works on capillary blood flow is given in this article. Some details are presented for two problems: the problem of deformation of the flexible red blood cells, their motion in the capillary blood vessels, and the pressure drop due to the red cell blood vessel interaction; and the problem of the flow of plasma ‘bolus’ between neighboring red cells.

The solution supplies many details about the microcirculation phenomenon. Taken together, a method is offered for the calculation of pressure drop in the capillary as a function of various physical parameters: the red cell volume per unit blood volume, (hematocrit), the ratio of the cell diameter to the blood vessel diameter, the ratio of the length of the blood vessel to its length, the volume of individual red cells, and a parameter relating the cell membrane elasticity, plasma viscosity and the cell velocity.     

Ultrastructural changes in erythrocytes and thrombocytes in patients with severe thermal burns of the skin in the burn shock period

The data obtained show that a great amount of deformed red blood cells, i.e. ovalocytes, cristate-shaped cells appear in the peripheral blood of patients with severe cutaneous burns during shock. In the most severe shocks a dramatic increase in degenerative forms of red blood cells in the blood has been observed. These are spheroids and spheroechynocytes frequently with impaired matrix structure. A correlation has been established between the progressing shock severity and the number of degenerative forms of red blood cells in the blood. Reversible changes of platelet fine structure were also noted.     

Characterization of mutations affecting embryonic hematopoiesis in the medaka, Oryzias latipes

In a genetic screen for mutations affecting organogenesis in the medaka, Oryzias latipes, we identified eight mutants with defects in embryonic hematopoiesis. These mutations were classified into seven complementation groups. In this paper, we characterize the five mutants that were confirmed in the next generation. The beni fuji mutant was defective in the generation of blood cells, exhibiting reduced blood cells at the initiation of circulation. Mutations in two genes, lady finger and ryogyoku, caused abnormal morphology of blood cells, i.e., deformation, along with a progressive decrease in the number of blood cells. The sekirei mutant exhibited photosensitivity with autofluorescent blood cells. Mutations in kyoho resulted in huge blood cells that were approximately three times longer than the wild-type blood cells. The spectrum of phenotypes identified in this study is similar to that of the zebrafish hematopoietic mutants except for the huge blood cells in kyoho. Our results demonstrate that medaka, as well as zebrafish, is a useful model to study hematopoiesis.     

Light- and Electronmicroscopic Observations on the Blood Cells of the Atlantic Hagfish,Myxine glutinosa (L.)

In the blood of Myxine glutinosa three cell lines may be distinguished: erythrocytes, granulocytes and agranulocytes. The erythrocytes are remarkably large, oval and nucleated. They are well defined in all their developmental stages by a characteristic micropinocytosis. They originate from blast cells which proliferate in the circulating blood. The blast cells probably form from agranulate stem cells of the intestinal myeloid tissue. The granulocytes constitute about half of the leucocytes. They are neutrophilic with a lobated nucleus. The granulocytopoiesis takes place in the intestinal myeloid tissue. The agranulocytes mainly include two cell types, termed spindle cells and lymphocyte-like cells. These cell types, however, transform into each other. Macrophages occur essentially in the peritoneal cavity rarely in the blood. Transition forms between macrophages and granulocytes may exist. The blood also contains cells which on morphological grounds have been termed thrombocytes. Whether these cells are identical with those necessary for clotting of the blood remains to be proved. With the exception of erythroblasts, the different lines of blast cells are difficult to identify and distinguish from each other. Possibly all lines of blood cells originate from agranulate lymphocyte-like stem cells, most of which are produced by the intestinal myeloid tissue.     

The repopulating potential and differentiation capacity of hematopoietic stem cells from the blood and bone marrow of normal mice

Using the hematopoietic colony technique, we have investigated the repopulating potential of bone marrow cells and leukocytes of blood from normal mice and have demonstrated that the frequency of hematopoietic stem cells in bone marrow is 50 to 150 times that of stem cells in the circulating blood. The differentiation capacity of these stem cells has also been examined. Results of comparative studies of the serial sections of hematopoietic colonies formed from marrow and blood leukocytes indicate that the differentiation capacity of stem cells from marrow and blood is similar, and that at least 80% of these cells differentiate along a single cell line. Thus, peripheral blood stem cells can effect a complete hematopoietic graft, establishing in the host, donor red cells, granulocytes, and platelets. The possibility that blood leukocytes may serve as a potential source of stem cells for hematopoietic transplants has been considered. Although blood contains stem cells, their frequency is so low as to make it unlikely that they would become a useful source of precursor cells for transplantation purposes.     

Abnormal flow properties of white blood cells in patients with severe ischaemia of the leg

The possible role of white blood cells in tissue ischaemia has attracted recent interest. White blood cells can block narrow vessels, particularly if perfusion pressure is reduced or if the cells become activated. To investigate the role of white blood cells in ischaemia microfiltration techniques were used to measure the flow properties of these cells in patients with severe leg ischaemia before and after amputation. Compared with controls white blood cells from patients showed impaired ability to flow through 8 μm and 5 μm pore filters. This applied to fractionated granulocytes and mononuclear cells as well as to unfractionated mixed white blood cells. White blood cells from blood draining the ischaemic leg had worse filterability than those from arm blood of the same patients. After amputation of the ischaemic leg there was definite improvement, the flow properties of the cells being no longer significantly different from controls.These abnormalities detected in white blood cells probably reflect activation of the cells by factors released in the ischaemic tissue. As activation alters the mechanical and adhesive properties of white blood cells, a vicious cycle of microcirculatory trapping at low perfusion pressure, activation, tissue damage, and further activation and trapping might contribute to the progressive worsening of tissue ischaemia.     

Red cell distribution and the recruitment of pulmonary diffusing capacity.

The distribution of red blood cells in alveolar capillaries is typically nonuniform, as shown by intravital microscopy and in alveolar tissue fixed in situ. To determine the effects of red cell distribution on pulmonary diffusive gas transport, we computed the uptake of CO across a two-dimensional geometric capillary model containing a variable number of red blood cells. Red blood cells are spaced uniformly, randomly, or clustered without overlap within the capillary. Total CO diffusing capacity (DLCO) and membrane diffusing capacity (DmCO) are calculated by a finite-element method. Results show that distribution of red blood cells at a fixed hematocrit greatly affects capillary CO uptake. At any given average capillary red cell density, the uniform distribution of red blood cells yields the highest DmCO and DLCO, whereas the clustered distribution yields the lowest values. Random nonuniform distribution of red blood cells within a single capillary segment reduces diffusive CO uptake by up to 30%. Nonuniform distribution of red blood cells among separate capillary segments can reduce diffusive CO uptake by >50%. This analysis demonstrates that pulmonary microvascular recruitment for gas exchange does not depend solely on the number of patent capillaries or the hematocrit; simple redistribution of red blood cells within capillaries can potentially account for 50% of the observed physiological recruitment of DLCO from rest to exercise.     

Effects of the butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) on the arylamines N-acetyltransferase activity in rat white blood cells

Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) were used to determine any effects on the N-acetyltransferase (NAT) activity in rat whole blood and white blood cells as measured by high performance liquid chromatography assay for the amounts of N-acetyl-2-aminofluorene (AAF) and 2-aminofluorene (AF). Two assay systems were performed, one with cellular cytosols, the other with intact white blood cells. The NAT activity in the whole blood and white blood cell cytosols was suppressed by BHA and BHT in a dose-dependent manner, i.e. the higher the concentrations of BHA and BHT, the higher the inhibition of NAT activity. Time-course experiments showed that NAT activity measured from the intact white blood cells was inhibited by BHA and BHT up to 24 h. The results suggest that BHA and BHT suppressed AF acetylation in rat blood with intact white blood cells.     

Immature T lymphocytes in human cord blood identified by monoclonal antibodies: a model for the study of the differentiation pathway of T cells in humans

The reactivity of human cord blood lymphocytes was assessed against a panel of monoclonal antibodies (MoAb). The mean proportion of OKT3+ cells (pan-T) was significantly lower in cord blood (52 +/- 13.8%; mean +/- SD) compared with that of adult blood (75 +/- 8.9%) and paralleled well with the E-rosette-forming capacity (50 +/- 16.3%). Both the proportions of OKT4+ cells (helper/inducer phenotype) and of OKT8+ cells (suppressor/cytotoxic phenotype) were significantly reduced in cord blood (43 +/- 11.8% vs 50.3 +/- 7.4% and 20 +/- 10.3% vs 25.6 +/- 6.0%, respectively), while the overall OKT4/OKT8 ratio was increased compared with adult blood (2.87 +/- 1.83 vs 2.04 +/- 0.61). Unlike adult blood, in 30 of the 35 samples of cord blood an overlap was observed between the total proportion of OKT4+ and OKT8+ cells (65 +/- 15.2%) and that of OKT3+ cells (52 +/- 14.3%). Although small numbers of cells coexpressing both antigens were occasionally found, double-staining analysis showed that the overlap in cord blood was mostly due to an expanded proportion of OKT3 (Leu-4)-/OKT8 (Leu-2)+ cells. Relevant proportions of OKT6+ (common thymocyte antigen) and OKT10+ (thymocytes, activated T cells, precursor cells) cells were found in cord blood as opposed to adult blood (10.8 +/- 8.6% vs 0.6 +/- 0.6% and 67 +/- 18.0% vs 8 +/- 2.1%, respectively), while terminal deoxynucleotidyl transferase-positive cells were observed only in two samples of cord blood. A small proportion of T cells (E-rosette+) reacted with the MoAb OKIa1 (HLA-DR). Finally, the proportion of cord blood cells recognized by the MoAb Leu-7 (HNK-1 clone) was almost negligible compared with adult blood (2.8 +/- 2.4% vs 15 +/- 7.5%). These data confirm the immaturity and heterogeneity of cord blood lymphocytes and demonstrate the presence at birth of circulating lymphocytes which express a surface phenotype reminiscent of that found in the late stages of intrathymic differentiation and in some human T-cell leukemias. Human cord blood may thus represent a suitable model for the study of the differentiation pathway of normal and pathological T-cells in humans.     

Evidence for a selective migration of fetus-specific CD4+CD25bright regulatory T cells from the peripheral blood to the decidua in human pregnancy

During pregnancy, the maternal immune system has to tolerate the persistence of fetal alloantigens. Many mechanisms contribute to the prevention of a destructive immune response mediated by maternal alloreactive lymphocytes directed against the allogeneic fetus. Murine studies suggest that CD4(+)CD25(+) T cells provide mechanisms of specific immune tolerance to fetal alloantigens during pregnancy. Previous studies by our group demonstrate that a significantly higher percentage of activated T cells and CD4(+)CD25(bright) T cells are present in decidual tissue in comparison with maternal peripheral blood in human pregnancy. In this study, we examined the phenotypic and functional properties of CD4(+)CD25(bright) T cells derived from maternal peripheral blood and decidual tissue. Depletion of CD4(+)CD25(bright) T cells from maternal peripheral blood demonstrates regulation to third party umbilical cord blood cells comparable to nonpregnant controls, whereas the suppressive capacity to umbilical cord blood cells of her own child is absent. Furthermore, maternal peripheral blood shows a reduced percentage of CD4(+)CD25(bright)FOXP3(+) and CD4(+)CD25(bright)HLA-DR(+) cells compared with peripheral blood of nonpregnant controls. In contrast, decidual lymphocyte isolates contain high percentages of CD4(+)CD25(bright) T cells with a regulatory phenotype that is able to down-regulate fetus-specific and fetus-nonspecific immune responses. These data suggest a preferential recruitment of fetus-specific regulatory T cells from maternal peripheral blood to the fetal-maternal interface, where they may contribute to the local regulation of fetus-specific responses.     

Tolerance-like condition developing in mice under the effect of antigen of erythrocyte lysate]

Lysate of sheep red blood cells obtained by the treatment of these cells with distilled water and purified by ultracentrifugation in cold possessed a weak immunogenicity. Its administration to mice caused the state of hyporeactivity to sheep red blood cells (a reduction of the immune response level to 10-25% of control. The capacity of the mise spleen cells to respond by immune reaction to the red blood cells following adoptive transfer was not disturbed. At the early periods after the lysate administrations the mouse spleen cells possessed a weak supressive activity in case of their transfer to the intact animals. The blood serum of mice treated with the lysate possessed a blocking activity which disappeared after the serum absorption with sheep red blood cells. A conclusion was drawn that hyporeactivity originating in mice after the lysate administration was caused by the presence in the serum of antibodies inhibiting the immune response.     

Selective release of antibody forming cells into the blood

Cells that are actively producing antibody in the spleen are not randomly released into the blood. At comparable times after immunization, the ratio of IgM/IgG antibody-producing cells in blood differs from that in the spleen and lymph nodes. In contrast to the primary response, a heightened number of antibody-producing cells in the lymphoid tissue during the secondary response is not reflected by an increased number in the blood. The findings suggest that some immunologically active cells are selectively retained by the lymphoid tissues while newly produced antibody-forming cells are released into the blood stream.     

Cell-autonomous and non-autonomous requirements for the zebrafish gene cloche in hematopoiesis.

Vertebrate embryonic hematopoiesis is a complex process that involves a number of cellular interactions, notably those occurring between endothelial and blood cells. The zebrafish cloche mutation affects both the hematopoietic and endothelial lineages from an early stage (Stainier, D. Y. R., Weinstein, B. M., Detrich, H. W. R., Zon, L. I. and Fishman, M. C. (1995) Development 121, 3141-3150). cloche mutants lack endocardium, as well as head and trunk endothelium, and nearly all blood cells. Cell transplantation studies have revealed that the endocardial defect in cloche is cell-autonomous: wild-type cells can form endocardium in mutant hosts, but mutant cells never contribute to the endocardium in wild-type or mutant hosts. In this paper, we analyze the cell-autonomy of the blood defect in cloche. The blood cell deficiency in cloche mutants could be an indirect effect of the endothelial defects. Alternatively, cloche could be required cell-autonomously in the blood cells themselves. To distinguish between these possibilities, we cotransplanted wild-type and mutant cells into a single wild-type host in order to compare their respective hematopoietic capacity. We found that transplanted wild-type cells were much more likely than mutant cells to contribute to circulating blood in a wild-type host. Furthermore, in the few cases where both wild-type and mutant donors contributed to blood in a wild-type host, the number of blood cells derived from the wild-type donor was always much greater than the number of blood cells derived from the mutant donor. These data indicate that cloche is required cell-autonomously in blood cells for their differentiation and/or proliferation. When we assessed early expression of the erythropoietic gene gata-1 in transplant recipients, we found that mutant blastomeres were as likely as wild-type blastomeres to give rise to gata-1-expressing cells in a wild-type host. Together, these two sets of data argue that cloche is not required cell-autonomously for the differentiation of red blood cells, as assayed by gata-1 expression, but rather for their proliferation and/or survival, as assayed by their contribution to circulating blood. In addition, we found that transplanted wild-type cells were less likely to express gata-1 in a mutant environment than in a wild-type one, suggesting that cloche also acts non-autonomously in red blood cell differentiation. This non-autonomous function of cloche in red blood cell differentiation may reflect its cell-autonomous requirement in the endothelial lineage. Thus, cloche appears to be required in erythropoiesis cell non-autonomously at a step prior to gata-1 expression, and cell-autonomously subsequently.     

Tunichrome content in the blood cells of the tunicate, Ascidia callosa Stimpson, as an indicator of vanadium distribution

Morula, compartment, signet ring, orange, lymphocyte and amoebocyte (granular and agranular) cells have been identified in the blood of A. callosa; in addition, nephrocytes have been described. Blood cell lysates contain a yellow chromogen with spectrophotometric and fluorimetric properties similar to tunichrome. The fluorescent characteristics of each of the seven blood cell types were determined using microspectrofluorimetry. Vanadium in A. callosa blood cells is primarily associated with tunichrome extracts, although lesser amounts are measurable in blood plasma and blood cell residues; both vanadium and tunichrome concentrations are in the order morula greater than compartment greater than signet ring cells.     

CD4 positive Leu-8 negative helper-inducer T cells predominate in the human intestinal lamina propria

The regulatory function of peripheral blood CD4 T cells correlates with the presence or absence of the membrane glycoprotein recognized by anti-Leu-8 antibody; CD4,Leu8- T cells help Ig synthesis and CD4,Leu-8+ T cells suppress Ig synthesis. In contrast to CD4 T cells from the peripheral blood and organized gut-associated lymphoid tissues, intestinal lamina propria CD4 T cells were found to have diminished expression of the Leu-8 Ag. Therefore, studies were performed to determine whether the decreased expression of the Leu-8 Ag on lamina propria CD4 T cells correlates with a difference in the ability of peripheral blood and lamina propria CD4 T cells to regulate PWM-stimulated Ig synthesis. At high T cell to non-T cell ratios, the helper function of lamina propria CD4 T cells was significantly higher than that of peripheral blood CD4 T cells. When CD4 T cells were incubated with anti-Leu-8 antibody, the suppressor function of peripheral blood CD4 T cells was increased, but lamina propria CD4 T cells did not suppress Ig synthesis. No difference was found between the helper function of CD4,Leu-8- T cells and the suppressor function of CD4, Leu-8+ T cells isolated from either the peripheral blood or the lamina propria. Thus, the difference in the regulatory function of CD4 T cells from the peripheral blood and the lamina propria is due to the quantitative difference in CD4,Leu-8+ T cells in these sites. Consequently, the intestinal lamina propria is a site enriched in CD4,Leu-8- T cells which predominantly mediate help for Ig synthesis.     

The role of the lymphoid system in the regulation of the blood glucose level.

Recent findings have led to a new hypothesis in which it is proposed that the immune system plays a role in regulating the increase in blood glucose levels after a meal. The relevant findings are: (1) the primary lymphoid tissue, the lymph nodes are mostly present within adipose tissue depots throughout the body (there are at least 12 such depots and about 10 (12) lymphocytes, 99% of which are present in lymph nodes); (2) lymphocytes and other immune cells utilize glucose at a high rate but almost all of it is converted to lactate which accumulates in the cells prior to release; (3) glutamine, some of which is synthesized in muscle from glucose, is utilized at a high rate by immune cells, the end-product of which is mainly aspartate, which also accumulates in the cells prior to release; and (4) finally, there is a common blood supply to the lymph node and the adipose tissue depot and the blood flow through the depot and hence the node is increased after a meal. It is proposed that, after a meal, some of the absorbed glucose is taken up from the blood by the lymphocytes and converted to lactate and glutamine is converted to aspartate. These are released slowly into the blood from where they are removed and converted to glycogen by the liver. Hence the immune cells provide a temporary buffer for glucose in the form of lactate and aspartate and, in this way, restrict the rise in blood glucose during and after a meal.     

Effect of phenylalanine- or tryptophan-loaded liposomes on the rheological properties of AA and SS erythrocytes

Phenylalanine or tryptophan was incorporated into AA and SS red blood cells by a liposomal transport system which was previously shown by Kumpati to inhibit and reverse sickling of intact SS red blood cells in vitro. In the present study, the effect of phenylalanine or tryptophan incorporation on the rheological properties was evaluated. The incorporation of phenylalanine or tryptophan into red blood cells decreased the viscosity of deoxy SS red blood cells which reached a level close to that for normal red blood cells due to the antisickling effect. These results demonstrate that this liposomal transport system which transferred phenylalanine or tryptophan into intact red cells and did not have any adverse effect on red cell metabolism or function did correct the viscosity of deoxy SS red cells by its antisickling effect. This method may have significant therapeutic implications in the treatment of sickle cell disease.     

Cell death and regeneration in the midgut of the mosquito, Culex quinquefasciatus

Haematophagy, the utilization of blood as food, has evolved independently among insects such as mosquitoes, bedbugs, fleas, and others. Accordingly, several distinct biological adaptations have occurred in order to facilitate the finding, ingestion and digestion of blood from vertebrate sources. Although blood meals are essential for survival and reproduction of these insects, mechanical and chemical stresses are caused by the ingestion of a sizable meal (frequently twice or more times the weight of the insect) containing large amounts of cytotoxic molecules such as haem. Here we present data showing that the stresses caused by a blood meal induce cell death in the midgut epithelium of Culex quinquefasciatus mosquitoes. The process involves apoptosis, ejection of dead cells to the midgut lumen and differentiation of basal regenerative cells to replace the lost digestive cells. The basal cell differentiation in blood-fed mosquito midguts represents an additional mechanism by which insects cope with the stresses caused by blood meals. C. quinquefasciatus adult females are unable to replace lost cells following a third or fourth blood meal, which may have a significant impact on mosquito longevity, reproduction and vectorial capacity.     

Time course of the age-related alterations in stored blood

The extent and time course of the impairments occurring in whole blood and erythrocyte cells stored under blood bank conditions were studied by monitoring the reduction of MAL-6 spin label added to the media containing whole blood or erythrocyte cells using electron spin resonance (ESR) technique. Impairments forming in the erythrocyte cells incubated for various times at 37 degrees C were also studied. Erythrocyte cells were found to undergo changes during the storage or incubation, leading to fast decay of MAL-6 spin labels signal height. The extent of the changes depends on storage or incubation time. However, the reduction in incubated or artificially aged erythrocyte (AAE) cells was faster than the reduction in whole blood (WB) and aged erythrocyte (AE) cells stored under blood bank conditions. Two exponential curves attributed to the liquid and cellular parts of a given samples were found to be described best in the reduction of MAL-6 spin label in WB, AE and AAE.