Molecular aspects of the interaction of albumin and tannined erythrocytes in the process of hemosensitization. II. The effect of temperature]

A study was made of a combined influence of the temperature of the medium and of sensitin concentration on the process of interaction of tannin-treated sheep erythrocytes and human serum albumin. On the basis of determination of the number of molecules bound by a single erythrocyte during hemosensitization,, depending on the mentioned conditions, it was revealed that the relative total albumin binding increased with the elevation of temperature. Elevation of temperature also led to the absolute and the relative increase in the stable and a reduction in the loose albumin binding by a single erythrocyte and the growth of sensitivity of the passive hemagglutination test. The role of chemical mechanisms in the erythrocyte albumin loading was demonstrated; this permitted to carry out erythrocyte albumin sensitization at a comparatively high temperature for the purpose of increasing the efficacy of passive hemagglutination test.     

Design of stable immunoglobulin erythrocyte diagnostica. 1. Erythocyte fixation and their sensitization by specific immunoglobulins]

The work presents the results of developing the method of fixation of erythrocyte constituting the cellular base of immunoglobulin erythrocytic diagnostic preparations and the sensitization of erythrocytes with immunoglobulin preparations of various specificity. Based on Ingraham's method, modified method of erythrocyte stabilization has been developed; it consists in the treatment of 50% cell suspension with 4% formaldehyde solution in the presence of 0.5% sucrose (erythrocyte suspension and formaldehyde solution being in the ratio 1 : 2.5). An economic and highly productive technique of sensitizing erythrocytes with immunoglobulin preparations has been developed. The essence of this technique lies in the interaction between 6% suspension of erythrocytes treated with formalin and tannin and the equal volume of sensitin taken in a working dose. The work also presents the method of synthesizing the bifunctional compound fluoro-borate bis-daizonium complex (obtained from benzidine) and discusses the comparative possibilities of the methods of developing immunoglobulin erythrocytic diagnostic preparations by sensitization of tannin-treated erythrocytes and by chemical conjugation.     

Heterogeneity of the cellular distribution of erythrocytic A antigens. Ultramicroscopic study]

A and A1 antigens have been detected on cells of the human erythrocyte series by immunoelectron microscopy. These antigens have been revealed by an indirect method involving various anti-A and anti-A1 antibodies (allo, auto, hetero-antibodies) and peroxidase-conjugated anti-immunoglobulin antibodies. Immunologic labelling has been carried out with erythrocyte or bone marrow cell suspensions which were fixed prior to incubation with reagents. Cells from various A phenotypes were examined. A and A1 antigens were visualized on maturing normoblasts, at every developmental stage. In addition cell to cell variations of the surface labelling of erythrocytes was found in normal phenotypes, suggesting the existence of several populations of cells according to antigenic load.     

Erythrocyte membrane antigen expression during friend cell differentiation: Analysis of two non-inducible variants

Erythrocyte membrane antigens have been detected on induced Friend erythroleukemic cells with a rabbit antiserum raised against mouse erythrocyte membranes. The antibody specificities of this antiserum have been quantitatively analyzed using a cellular radioimmunoassay. After absorption with thymocytes, the rabbit anti-erythrocyte membrane serum bound to dimethylsulfoxide (DMSO)-induced Friend erythroleukemic cells and to mouse erythrocytes but not to uninduced Friend cells or thymocytes. Reciprocal inhibition studies demonstrated that, following complete thymocyte absorption, the antiserum detected similar antigenic specificities, termed erythrocyte membrane antigens (EMA), on both mature erythrocytes and induced Friend cells. The expression of these erythrocyte membrane antigens was also induced on Friend cells by other agents, such as ouabain and dimethylacetamide (DMA). In contrast, exogenous hematin, which did not induce hemoglobin synthesis in the Friend cell clones used in this study, also did not induce erythrocyte membrane antigen expression. Two independently derived variant clones which do not produce hemoglobin in reponse to DMSO were analyzed for their ability to produce erythrocyte membrane antigens in response to various inducers of Friend cell differentiation. Clone TG-13 is not inducible by DMSO or hematin but is weakly induced by DMA for both hemoglobin production and erythrocyte membrane antigen expression. Another variant clone, M18, was also analyzed. This clone does not synthesize detectable hemoglobin when grown in either DMSO or hematin alone, but undergoes extensive hemoglobin synthesis when grown in medium containing both DMSO and hematin. M18 does, however, express erythrocyte membrane antigens when grown in DMSO alone: the presence of hematin and DMSO together in the growth medium does not enhance expression of these antigens. Thus M18 appears to be defective for hemoglobin inducibility, and this defect can be overcome by exogenous hematin; however, the expression of erythrocyte membrane antigens is not affected by this block in hemoglobin synthesis. The results with the variant clones are discussed in terms of a program for Friend cell differentiation in which the induction of hemoglobin synthesis and erythrocyte membrane antigen expression are under both co-ordinate and separate controls.     

Storage-induced changes in erythrocyte membrane proteins promote recognition by autoantibodies

Physiological erythrocyte removal is associated with a selective increase in expression of neoantigens on erythrocytes and their vesicles, and subsequent autologous antibody binding and phagocytosis. Chronic erythrocyte transfusion often leads to immunization and the formation of alloantibodies and autoantibodies. We investigated whether erythrocyte storage leads to the increased expression of non-physiological antigens. Immunoprecipitations were performed with erythrocytes and vesicles from blood bank erythrocyte concentrates of increasing storage periods, using patient plasma containing erythrocyte autoantibodies. Immunoprecipitate composition was identified using proteomics. Patient plasma antibody binding increased with erythrocyte storage time, while the opposite was observed for healthy volunteer plasma, showing that pathology-associated antigenicity changes during erythrocyte storage. Several membrane proteins were identified as candidate antigens. The protein complexes that were precipitated by the patient antibodies in erythrocytes were different from the ones in the vesicles formed during erythrocyte storage, indicating that the storage-associated vesicles have a different immunization potential. Soluble immune mediators including complement factors were present in the patient plasma immunoprecipitates, but not in the allogeneic control immunoprecipitates. The results support the theory that disturbed erythrocyte aging during storage of erythrocyte concentrates contributes to transfusion-induced alloantibody and autoantibody formation.     

Intracellular reduced glutathione content in normal and type 2 diabetic erythrocytes: effect of insulin and (-)epicatechin.

Catechins, polyphenolic compounds belonging to flavanoid family, have been reported to posses insulin-like properties and their antidiabetic actions have also been documented. Recently catechins have received much attention as strong anti-oxidative agents. Since oxidative stress has been implicated in the development of diabetic complications and GSH plays an important role in protection against oxidative damages, we have studied the in vitro effect of (-)epicatechin and insulin on the reduced glutathione content in normal and type 2 diabetic erythrocytes. The GSH content was significantly lower (p < 0.001) in type 2 diabetic patients as compared to normal individuals. In vitro insulin treatment (10(-9) M) resulted in increase in the GSH content in both normal and type 2 diabetic erythrocytes. (-)Epicatechin (1mM) also resulted in an increase in erythrocyte GSH content in both normal and type 2 diabetic erythrocytes. Insulin gave a pronounced dose-responsive effect: maximum increase in GSH content at physiological hormone concentration and a lower increase at higher and lower insulin concentrations. (-)Epicatechin did not show a similar dose-responsive effect. Although the exact mechanism by which (-)epicatechin causes elevation of erythrocyte GSH is not clear nevertheless this finding may have important therapeutic implications. A higher content of dietary flavanoids may thus protect diabetic patients against long-term complications.     

Cytotoxic effect of poly-dispersed single walled carbon nanotubes on erythrocytes in vitro and in vivo

Single wall Carbon Nanotubes (SWCNTs) are hydrophobic and do not disperse in aqueous solvents. Acid functionalization of SWCNTs results in attachment of carboxy and sulfonate groups to carbon atoms and the resulting acid functionalized product (AF-SWCNTs) is negatively charged and disperses easily in water and buffers. In the present study, effect of AF-SWCNTs on blood erythrocytes was examined. Incubation of mouse erythrocytes with AF-SWCNTs and not with control SWCNTs, resulted in a dose and time dependent lysis of erythrocyte. Using fluorescence tagged AF-SWCNTs, binding of AF-SWCNTs with erythrocytes could be demonstrated. Confocal microscopy results indicated that AF-SWCNTs could enter the erythrocytes. Treatment with AF-SWCNTs resulted in exposure of hydrophobic patches on erythrocyte membrane that is indicative of membrane damage. A time and dose dependent increase in externalization of phosphatidylserine on erythrocyte membrane bilayer was also found. Administration of AF-SWCNTs through intravenous route resulted in a transient anemia as seen by a sharp decline in blood erythrocyte count accompanied with a significant drop in blood haemoglobin level. Administration of AF-SWCNTs through intratracheal administration also showed significant decline in RBC count while administration through other routes (gavage and intra-peritoneal) was not effective. By using a recently developed technique of a two step in vivo biotinylation of erythrocytes that enables simultaneous enumeration of young (age <10 days) and old (age>40 days) erythrocytes in mouse blood, it was found that the in vivo toxic effect of AF-SWCNTs was more pronounced on older subpopulation of erythrocytes. Subpopulation of old erythrocytes fell after treatment with AF-SWCNTs but recovered by third day after the intravenous administration of AF-SWCNTs. Taken together our results indicate that treatment with AF-SWCNTs results in acute membrane damage and eventual lysis of erythrocytes. Intravenous administration of AF-SWCNTs resulted in a transient anemia in which older erythrocytes are preferably lysed.     

Beneficial influence of dietary curcumin, capsaicin and garlic on erythrocyte integrity in high-fat fed rats

In rats rendered hyperlipidemic by maintaining them on a high-fat diet (30%) for 8 weeks, inclusion of spice principles [curcumin (0.2%) or capsaicin (0.015%)] or garlic (2.0%) in the diet produced significant hypotriglyceridemic effect. Plasma cholesterol remained unaffected in high-fat treatment. Hepatic triglyceride content was significantly higher in high-fat fed rats, and this increase was effectively countered by inclusion of the hypolipidemic spice agents -- curcumin, capsaicin or garlic in the diet. The lipid profile of erythrocyte membranes of hyperlipidemic rats was similar to basal controls. An examination of the osmotic fragility of erythrocytes in various groups indicated that the red blood cells of hyperlipidemic rats display a slight resistance to osmotic lysis. Inclusion of spice principles [curcumin (0.2%) or capsaicin (0.015%)] or garlic (2.0%) in the diet, which produced the hypotriglyceridemic effect, appeared to beneficially correct this altered osmotic fragility of erythrocytes. Activities of ouabain-sensitive Na(+),K(+)-ATPase as well as acetylcholinesterase of erythrocyte membranes in high-fat fed rats remained unaltered. Activity of Ca(2+),Mg(2+)-ATPase in erythrocyte membrane was significantly decreased in high-fat fed animals, whereas dietary spice principles and garlic countered this reduction in enzyme activity. In the absence of any change in the cholesterol/phospholipid molar ratio in the erythrocyte membrane, a decreased activity of membrane-bound Ca(2+),Mg(2+)-ATPase could have probably contributed to the accumulation of intracellular calcium leading to the diminished deformability of the erythrocytes in high-fat fed rats.     

Functional and structural changes in the surface of human erythrocytes after irradiation with UV rays of various wave lengths. I. The expression of ABO and rhesus system antigens

UV irradiation (254 nm) in doses increasing erythrocyte haemolysis by 5, 10, 18 and 28 per cent was found to stimulate, by 2--16 times, the agglutination activity of ABO and Rh system antigens. The stimulation effect was the higher the lower the antigen activity before irradiation. In the Rh-negative (Rh-) erythrocytes, irradiation induced manifestation of the Rh0(D)-antigen specific activity suggesting that this antigen may be present in the Rh- erythrocyte membrane. The expression of Rh0(D)-antigen in Rh- erythrocytes, the stimulation of its activity in Rh-positive cells, and the activation of ABO system antigens may result from a photochemical destruction of the outer perimembraneous layer and release some of its components which stain in situ with alcian blue to be presumably glycoproteins. This effect is necessary to keep in mind when UV-irradiated blood transfusion is performed in therapeutic aims Rh- patients.     

Comparative study of inhibition of mannose-resistant haemagglutination caused by CFA/I, CFA/II, K88 and K99-positive Escherichia coli strains

Abstract We have studied the inhibition of mannose-resistant haemagglutination (MRHA) caused by Escherichia coli strains with CFA/I, CFA/II, K88, K99 and by other faecal E. coli lacking these colonisation antigens, by means of 30 sugar compounds and by enzymatic treatment of erythrocytes with neuraminidase, α-mannosidase, β-galactosidase, trypsin and pronase, and with formaldehyde. Inhibition of MRHA by sugars was effective only in K88-positive strains with d (+)glucosamine, mucic acid and bovine submaxillary mucin. Enzymatic treatment and the formolisation of erythrocytes gave different results on MRHA activity in strains possessing each colonisation antigen type. Results suggest that the erythrocyte receptor for CFA/I and CFA/II may possibly be sialoglycoprotein in which N -acetylneuraminic acid (NANA) plays an important role, because MRHA activity in these strains was inhibited by treatment of erythrocytes with neuraminidase and pronase. On the other hand, erythrocyte receptors for K88 and K99, like receptors for haemagglutinins of faecal E. coli lacking these colonization antigens, may have other glycoconjugate structures in which proteins and NANA are not essential. Our observations also suggest that the nature (or structure) of the receptor for a specific colonisation antigen on diverse erythrocyte types may be different.     

Studies on the effects of lipopolysaccharide on lipid peroxidation of erythrocyte and its reversal by mannitol and glycerol.

Gram-negative sepsis often produces endotoxin (LPS) which causes infection. Reduction in tissue perfusion due to microcirculatory failure may lead to septic shock. We studied the effect of LPS on lipid peroxidation of erythrocyte. In vitro studies using 50 microg to 250 microg LPS/ml blood showed increased lipid peroxidation of erythrocyte in a dose-dependent manner. The increased effect of lipid peroxidation does not occur with LPS when erythrocytes were washed to remove plasma and leukocytes. Mannitol and glycerol, known scavengers of hydroxyl radical, arrest the elevation in lipid peroxidation of erythrocytes after LPS treatment. Hemolysis of erythrocytes was reduced with low doses of LPS. Plasma lipid peroxidation was elevated after treatment of blood with LPS. From the results we suggest that the peroxidation of erythrocyte lipid caused by LPS may probably play a role in the production of septic shock.     

MHC class I antigens as surface markers of adult erythrocytes during the metamorphosis of Xenopus

An alloantiserum produced against Xenopus MHC class I antigens has been used to distinguish different erythrocyte populations at metamorphosis. By analysis using a fluorescence-activated cell sorter (FACS) analyzer, tadpole (stage 55) and adult erythrocytes have distinct volume differences and tadpole cells have no MHC antigens on the cell surface. Both tadpole and adult erythrocytes express a "mature erythrocyte" antigen marker, recognized by its monoclonal antibody (F1F6). During metamorphosis, immature erythrocytes, at various stages of differentiation, which express adult levels of cell-surface MHC antigens by 12 days after tail resorption, are found in the bloodstream. These immature cells are biosynthetically active, produce adult hemoglobin, and mature by 60 days after the completion of metamorphosis. Percoll gradient-density fractionation has shown that all of the cells in the new erythrocyte series express adult levels of MHC antigens but there is only a gradual increase in the amount of "mature erythrocyte" antigen. Tadpole erythrocytes, which are biosynthetically active during larval stages, produce small amounts of surface MHC antigens before the metamorphic climax and then become metabolically inactive. They are completely cleared from the circulation by 60 days after metamorphosis. Erythrocytes from tadpoles arrested in their development for long periods of time express intermediate levels of MHC antigens, suggesting a "leaky" expression of these molecules in the tadpole cells. The most abundant erythrocyte cell-surface proteins from tadpoles and adults, as judged by two-dimensional gel electrophoresis, are very different.     

Mode of transport and possible mechanism of action of l-phenylalanine benzyl ester as an anti-sickling agent

l-Phenylalanine benzyl ester (Phe-Bz) and a number of ester analogues prevent sickling of erythrocytes from sickle cell disease patients. The compounds tested exhibit anti-sickling activity in the concentration range 0.5–3.0 mM. A general feature of these compounds is the presence of two aromatic rings in their molecular structure. The anti-sickling agents rapidly enter the erythrocyte and are hydrolysed to their component molecules. Incubation of human erythrocytes with 3.0 mM l-phenylalanine for 30 min at 37°C results in accumulation of 2.0 mmol l-phenyalanine/l cells, while incubation of erythrocytes with 3.0 mM Phe-Bz under similar conditions results in the production of 4.0 mmol l-phenylalanine/l cells and an equivalent amount of benzyl alcohol. Both l-phenylalanine and benzyl alcohol are inhibitors of the gelation of deoxyhaemoglobin S (deoxy-HbS) in vitro. Moreover, Phe-Bz and related anti-sickling agents fluidize the lipid bilayer of the erythrocyte membrane, inhibiting several transport systems, including those for l-phenylalanine, uridine and sulphate ions, as well as the Na⁺ pump and the Na⁺/K⁺ cotransporter, but increasing the passive influx and efflux of both cations and anions. The accumulation of Phe-Bz hydrolysis products within the erythrocyte together with the effects of Phe-Bz on cation permeability result in the influx of water causing the cell to swell. Thus, treatment of erythrocytes with 3.0 mM Phe-Bz at 37°C for 30 min causes an increase in mean cell volume of 14.8%, decreasing the mean intracellular haemoglobin concentration from 34 to 29.6 g%. The increase in cell volume caused by Phe-Bz and its analogues together with the direct effects of their hydrolysis products on HbS probably act in concert to bring about the anti-sickling effect.     

Mode of transport and possible mechanism of action of l-phenylalanine benzyl ester as an anti-sickling agent

l-Phenylalanine benzyl ester (Phe-Bz) and a number of ester analogues prevent sickling of erythrocytes from sickle cell disease patients. The compounds tested exhibit anti-sickling activity in the concentration range 0.5–3.0 mM. A general feature of these compounds is the presence of two aromatic rings in their molecular structure. The anti-sickling agents rapidly enter the erythrocyte and are hydrolysed to their component molecules. Incubation of human erythrocytes with 3.0 mM l-phenylalanine for 30 min at 37°C results in accumulation of 2.0 mmol l-phenyalanine/l cells, while incubation of erythrocytes with 3.0 mM Phe-Bz under similar conditions results in the production of 4.0 mmol l-phenylalanine/l cells and an equivalent amount of benzyl alcohol. Both l-phenylalanine and benzyl alcohol are inhibitors of the gelation of deoxyhaemoglobin S (deoxy-HbS) in vitro. Moreover, Phe-Bz and related anti-sickling agents fluidize the lipid bilayer of the erythrocyte membrane, inhibiting several transport systems, including those for l-phenylalanine, uridine and sulphate ions, as well as the Na⁺ pump and the Na⁺/K⁺ cotransporter, but increasing the passive influx and efflux of both cations and anions. The accumulation of Phe-Bz hydrolysis products within the erythrocyte together with the effects of Phe-Bz on cation permeability result in the influx of water causing the cell to swell. Thus, treatment of erythrocytes with 3.0 mM Phe-Bz at 37°C for 30 min causes an increase in mean cell volume of 14.8%, decreasing the mean intracellular haemoglobin concentration from 34 to 29.6 g%. The increase in cell volume caused by Phe-Bz and its analogues together with the direct effects of their hydrolysis products on HbS probably act in concert to bring about the anti-sickling effect.     

Lactoferrin stimulates erythrocyte Na+/K+ -adenosine triphosphatase: effect of some modulators of membrane phosphorylation

We studied the effect of some modulators of signal transduction on the erythrocyte Na+/ K+-ATPase. Go6976 and Go6983 (protein kinase C inhibitors) showed a stimulatory effect and calyculin A (protein phosphatase inhibitor) exerted an inhibitory effect on the Na pump activity. Some of the tested modulators of cell-signaling [protein phosphatase(s), phosphodiesterase, calmodulin and some protein kinases] interfered with the lactoferrin (Lf) stimulatory effect on the sodium pump. Lf itself was able to modulate the effect of some agents upon the pump activity. Moreover, an additive effect of stimulation was found when Lf and some agents were used simultaneously. The summarized results showed that: (i) Lf upregulates the Na+/K+-ATPase in erythrocytes and facilitates the K+ influx into the erythrocytes; (ii) the effect of pump stimulation is mediated by phosphorylation processes. These results suggest a potential opportunity for using Lf alone or together with other agents as a stimulator of the erythrocyte Na+/K+-ATPase.     

Plasmodium lipid rafts contain proteins implicated in vesicular trafficking and signalling as well as members of the PIR superfamily, potentially implicated in host immune system interactions

Plasmodium parasites, the causal agents of malaria, dramatically modify the infected erythrocyte by exporting parasite proteins into one or multiple erythrocyte compartments, the cytoplasm and the plasma membrane or beyond. Despite advances in defining signals and specific cellular compartments implicated in protein trafficking in Plasmodium-infected erythrocytes, the contribution of lipid-mediated sorting to this cellular process has been poorly investigated. In this study, we examined the proteome of cholesterol-rich membrane microdomains or lipid rafts, purified from erythrocytes infected by the rodent parasite Plasmodium berghei. Besides structural proteins associated with invasive forms, we detected chaperones, proteins implicated in vesicular trafficking, membrane fusion events and signalling. Interestingly, the raft proteome of mixed P. berghei blood stages included proteins encoded by members of a large family (bir) of putative variant antigens potentially implicated in host immune system interactions and targeted to the surface of the host erythrocytes. The generation of transgenic parasites expressing BIR/GFP fusions confirmed the dynamic association of members of this protein family with membrane microdomains. Our results indicated that lipid rafts in Plasmodium-infected erythrocytes might constitute a route to sort and fold parasite proteins directed to various host cell compartments including the cell surface.     

Erythrocytes participate significantly in blood transport of amino acids during the post absorptive state in normal humans

To investigate the participation of erythrocytes in the blood transport of amino acids during the course of intestinal absorption in humans, erythrocyte and plasma amino-acid concentrations were determined following ingestion of an oral load of amino acids. In addition to baseline plasma and erythrocyte amino acid concentrations in 18 subjects, plasma and erythrocyte amino acids kinetics during the 125 min following an oral amino acid load were further determined in 9 of the 18 subjects. The results showed that human erythrocytes contained most amino acids at similar or higher concentrations than plasma. Furthermore, the correlations observed between plasma and erythrocyte contents clearly indicated that erythrocytes were involved in the transport of amino acids by the blood. For some amino acids erythrocyte transport sometimes exceeded that of plasma. Significant correlation coefficients showed that strong plasma-erythrocyte relationships existed for alanine, valine, methionine, isoleucine, leucine, phenylalanine, and ornithine. In conclusion, our data supported the hypothesis that both blood compartments, plasma and erythrocytes, are involved significantly in the blood transport of amino acids in humans during the postabsorptive state. Accepted: 24 June 1998     

Extracorporeal immunostimulating effect of terrilytin and lysozyme]

The role of splenocytes and erythrocytes in showing an extracorporal action by terrilytin and lysozyme was studied. The extracorporal effect of terrilytin was to a greater extent mediated by the spleen cells adhering to the plastic while the extracorporal effect of lysozyme was mainly mediated by the heavy ("old") erythrocytes. The heat treatment at a temperature of 42 degrees C for 15 minutes did not abolish the terrilytin extracorporal effect mediated by the erythrocytes but completely abolish the similar effect induced by lysozyme which bound to the erythrocyte membrane. After exposure of the erythrocytes to terrilytin, the strength of the lysozyme binding increased and there was a respective increase in the immunostimulating activity of the erythrocytes.     

Changes in the passive electrical properties of the erythrocytes during hemosorption

Passive electrical properties of erythrocytes were studied during hemosorption in vivo. It was shown that specific conduction and capacity of the erythrocyte plasma membrane were reduced after hemosorption. Incubation of erythrocyte suspension with free fatty acids resulted in an increase in specific conduction and capacity of the plasma membrane. That effect was eliminated after the passing of erythrocytes through a column with activated charcoal.     

Serological studies on the blood of the primates: iii.distribution of serological factors related to human isoagglutinogens in the blood of lower monkeys

During the differentiation and maturation of erythrocytes, the surface molecules of erythrocytes are gradually expressed and stabilized. These molecules are to be antigenic in addition to their functions of maintain-ing cell membrane structural stability, material transport and exchange of cells and signal transmission between cells. The antigenic molecules on the erythrocyte surface are called erythrocyte blood group antigens. The blood group antigens and their corresponding blood group antibodies in vivo are important indicators for clinical blood transfusion and organ transplantation, and also form the basis for research on blood group related diseases. Three hundred and sixty-eight erythrocyte blood group antigens have been confirmed so far, which are classified into 39 blood group systems, 5 blood group collections and 2 blood group series. Based on the diversity of blood group antigens and their composition of glycolipids, glycoproteins and other molecules, this study mainly reviews the classification, molecular structure, antibody response and gene regulation of blood group antigens, and explains the main reasons for the diversity of blood group antigens.