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PubMed1998

[Differentiation and maturation of erythroblasts].

Erythropoietin/receptor (EPO/EPOR) system is a pivotal regulator of erythropoiesis. Indeed, EPO-deficient and EPOR-deficient mice are embryonic lethal. The EPOR has two dominant forms, a full-length one (EPOR-F) and a truncated one (EPOR-T), by an alternative splicing mechanism of mRNA. The EPOR-T expresses abundantly in more immature erythroid progenitor cells. The EPOR-T acts as a dominant negative regulator of EPO-signals for proliferation and anti-apoptosis in cell lines. Presumably, the EPOR-T forms a heterodimer with EPOR-F and results in inhibition of efficient EPO-signals. Transgenic mice over-expressing the EPOR-T show an anemia and a severe defect in recovery from acute anemia. This result strongly suggests that the EPOR-T acts as a negative regulator for erythropoiesis also in vivo. It was reported that a large number of erythroid precursor cells die of apoptosis under physiological concentration of EPO in mouse. At higher EPO-concentration, these erythroid precursors escape from apoptosis and mature into erythrocytes. This mechanism might allow immediate supply of a large number of erythrocytes in case of acute anemia. In such mechanism, the EPOR-T might play an important role as a regulator of EPO-induced signals in erythroid cells.

Animals↗

PubMed1992

Detecting of the minimal residual disease contaminated in peripheral blood stem cell transplantation in the B-cell malignant lymphoma patients.

For sufficient collection of hemopoietic stem cells from peripheral blood for autologous peripheral blood stem cell transplantation (PBSCT), four patients with B-cell-type non-Hodgkin lymphoma (B-NHL) were examined for the appearance of circulating hemopoietic progenitors in blood (PSC) during the hemopoietic recovery phase following marrow ablative therapy in combination with or without administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). Each patient received only chemotherapy in the first course, and rhG-CSF (1 microgram/kg/day) was administered for 14 consecutive days from the last day of the second chemotherapy. In the second chemotherapy course with rhG-CSF administration, white blood cell (WBC) counts demonstrated two peaks, and the appearance of granulocyte-macrophage precursor cells (CFU-GM) in blood at the maximum level was coincident with the second peak of WBC elevation. Erythroid precursor cells (BFU-E) were also detectable in blood after chemotherapy but the peak level was not enhanced by the use of rhG-CSF. To determine whether the minimal residual disease (MRD) cells were contaminated in PSC corrected from blood, kappa-lambda imaging (KLI) analysis was performed to detect the malignant B-cell population (mBp) before and after chemotherapy. No mBp was found in two of four patients in blood, although three of them were involved with mBp in bone marrow. The presence of mBp was detected in two patients both before and after chemotherapy, even though these cells were hardly detected morphologically, suggesting the necessity of judging for the incidence of contamination of MRD cells when collecting PSCs.

Adult↗

PubMed1986

Partial spectrin deficiency in hereditary pyropoikilocytosis.

Hereditary pyropoikilocytosis (HPP) is a severe hemolytic anemia in which an instability of the red cell membrane skeleton has been correlated with structural and functional defects of spectrin. We now report that 13 unrelated HPP subjects have approximately 30% less spectrin than normal as evidenced by a decreased spectrin/band 3 ratio. We also examine the role of spectrin degradation as an underlying cause of this partial spectrin deficiency. Our studies demonstrate that the reduced spectrin content of HPP red cells remains constant during in vivo aging of the cells in the peripheral blood, as well as during in vitro incubation. Furthermore, immunoblotting experiments using an affinity-purified antispectrin antibody indicate that there is no loss of spectrin during membrane preparation and also that neither whole HPP red cells nor ghosts nor cytosol contains any abnormal spectrin degradation products. These data suggest that spectrin is not degraded and that it is stable on the membrane of the circulating HPP red cell. In contrast, however, incubation of free spectrin with a lysate of nucleated erythroid precursor cells indicates that HPP alpha I/46 spectrin, but not HPP alpha I/74 spectrin, is more susceptible to proteolytic degradation than a control. These data imply that the decreased spectrin content of HPP is not due to a single defect but that a more complex mechanism is involved. In HPP Sp alpha I/46 subjects, an increased proteolytic degradation in bone marrow erythroid precursors of cytosolic spectrin, prior to its assembly on the membrane, could contribute toward the partial spectrin deficiency.

Anemia, Hemolytic↗

PubMed1996

Erythropoietin in mouse avascular yolk sacs is increased by retinoic acid.

Erythropoiesis begins first in the visceral yolk sac (VYS) of the embryo; however, the involvement of erythropoietin (EPO) in yolk-sac erythropoiesis has not been studied adequately. This study reports the expression of EPO in normal and hypoxic VYSs and alterations in yolk sac components induced by retinoic acid (RA) in mice. Gravid mice (plug day = day 0 of gestation) were given one oral dose of 60 mg/kg of RA in olive oil on days 6, 6.5, 7, 7.5, or 8 of gestation and were sacrificed 2.5, 3, or 3.5 days later. Control mice received olive oil without RA. None of the dams developed anemia, but more than 80% of the embryos of the dams that received RA on day 6, 6.5, or 7 of gestation had avascular yolk sacs (AVYs) and anemia. In these AVYs, the adenosine triphosphate (ATP) level was as low as 18-59% of that in the control VYSs. Reverse transcription-polymerase chain reaction and Southern analysis of products demonstrated that mRNA for EPO receptor (EPR) was expressed in both VYSs and AVYs on days 9-11 of gestation, and EPO mRNA was present in VYSs and AVYs on days 9 and 10 of gestation and in vehicle-exposed VYSs on day 11 of gestation. Furthermore, enzyme immunoassay of EPO indicated that AVYs contained more EPO protein than control VYSs. Light microscopy revealed that, in AVYs, in addition to the defective hemopoietic cells, the endodermal layer was exclusively altered: The presence of focal proliferated regions and the separation from the mesenchyme led to a single layer from which some immature cells seemed to be migrating. Immunolocalization of EPO showed its presence in all components of VYSs with a characteristic distribution pattern: In the endodermal layer, cells with positive EPO staining decreased as gestation advanced, and erythroid precursor cells showed positive staining. In AVYs, the proliferated endodermal cells had EPO in abundance; in the separated regions, the distinction between positive and negative EPO staining became clearer than that in the control VYSs, and the immature cells in the lumens also had EPO. EPR was seen on the cell surface of the corresponding cells that reacted to EPO. These findings suggest that VYSs not only produce EPO temporarily but also respond to the oxygen content in situ. EPO and EPR appear to be synthesized in the endodermal cells of the VYSs that are likely to respond to the circumstances induced by RA.

Adenosine Triphosphate↗

PubMed2006

Hemoglobin is expressed by alveolar epithelial cells.

Hemoglobin gene expression in non-erythroid cells has been previously reported in activated macrophages from adult mice and lens cells, and recent studies indicate that alveolar epithelial cells can be derived from hematopoietic stem cells. Our laboratory has now produced strong evidence that hemoglobin is expressed by alveolar type II (ATII) cells and Clara cells, the primary producers of pulmonary surfactant. ATII cells are also closely involved in innate immunity within the lung and are stem cells that differentiate into alveolar type I cells. Reverse transcriptase-PCR was used to measure the expression of transcripts from the alpha- and beta-globin gene clusters in several human and rodent pulmonary epithelial cells. Surprisingly, the two major globin mRNAs characteristic of adult erythroid precursor cells were clearly expressed in human A549 and H441 cell lines, mouse MLE-15 cells, and primary ATII cells isolated from normal rat and mouse lungs. DNA sequencing verified that these PCR products were indeed the result of specific amplification of globin gene cDNAs. These alveolar epithelial cells also expressed the corresponding hemoglobin protein subunits as determined by Western blotting, and tandem mass spectrometry sequencing was used to verify the presence of both alpha- and beta-globin polypeptides in rat primary ATII cells. The function of hemoglobin expression by cells of the pulmonary epithelium will be determined by future studies, but this novel finding could potentially have important implications for the physiology and pathology of the lung.

Adult↗

PubMed1988

Effect of age on some properties of mice erythrocytes.

The hematological parameters of young (2-month-old) and old (2-year-old) mice were compared. No differences could be detected with the exception of an increased percentage of reticulocytes in the old animals suggesting that anemia in senescent mice does not occur. Red blood cell mean half-life in old mice was 8 +/- 0.8 days compared to 12 +/- 1 days in young mice. This reduced survival of red blood cell is not due to a different rate of cell phagocytosis in the reticulohistiocytic system of young and old animals since erythrocytes from young mice have the same mean half-life when injected both in young and old animals and vice versa. Thus, the old mice have a reduced red cell life-span but the same hematocrit of the young, suggesting that old animals possess a chronologically younger population of erythrocytes than do young animals. This has been confirmed by measuring the specific activities of some red blood cell age-dependent enzymes (hexokinase, glucose-6-phosphate dehydrogenase, pyruvate kinase) that were found to be higher in the older animals, and by the separation of erythrocytes into different density (age) groups by Percoll/albumin density gradient centrifugation. However, the erythrocytes osmotic fragility, and the cellular contents of adenine and pyridine nucleotides, as well as the content of 2,3-diphosphoglycerate and reduced glutathione, show that circulating erythrocytes in old animals constitute an heterogeneous cell population whose properties cannot be explained on the basis of a chronologically younger erythrocyte population. Furthermore, evaluation of cell components in hemopoietic tissues have shown an increased porportion of erythroid precursor cells in old animals confirming that old mice compensate for reduced red cell survival with an increased erythropoiesis.

Aging↗

PubMed1995

Localization of specific erythropoietin binding sites in defined areas of the mouse brain.

The main physiological regulator of erythropoiesis is the hematopoietic growth factor erythropoietin (EPO), which is induced in response to hypoxia. Binding of EPO to the EPO receptor (EPO-R), a member of the cytokine receptor superfamily, controls the terminal maturation of red blood cells. So far, EPO has been reported to act mainly on erythroid precursor cells. However, we have detected mRNA encoding both EPO and EPO-R in mouse brain by reverse transcription-PCR. Exposure to 0.1% carbon monoxide, a procedure that causes functional anemia, resulted in a 20-fold increase of EPO mRNA in mouse brain as quantified by competitive reverse transcription-PCR, whereas the EPO-R mRNA level was not influenced by hypoxia. Binding studies on mouse brain sections revealed defined binding sites for radioiodinated EPO in distinct brain areas. The specificity of EPO binding was assessed by homologous competition with an excess of unlabeled EPO and by using two monoclonal antibodies against human EPO, one inhibitory and the other noninhibitory for binding of EPO to EPO-R. Major EPO binding sites were observed in the hippocampus, capsula interna, cortex, and midbrain areas. Functional expression of the EPO-R and hypoxic upregulation of EPO suggest a role of EPO in the brain.

Animals↗

PubMed1999

Infection of apheresis cells by parvovirus B19.

Parvovirus B19 is the only member of the Parvoviridae family known to cause disease in humans. Owing to the high level of cell tropism the virus can only replicate in proliferating and differentiating erythroid precursor cells, which are present in human bone marrow and foetal liver. As human bone marrow is very difficult to obtain, an alternative in vitro system for the propagation of B19 virus has been developed, based on the application of mobilized haemapoietic progenitor (apheresis) cells. These cells are routinely harvested from cancer patients after treatment with recombinant human granulocyte/macrophage colony-stimulating factor. Replication of parvovirus B19 in vitro is possible in these cells after stimulation with erythropoietin. Therefore, this system is an easily, accessible alternative to the use of human bone marrow in parvovirus B19 infection assays.

Blood Component Removal↗

PubMed1990

Tests for genotoxicity: principles and findings in relation to omeprazole.

Omeprazole has been subjected to an unusually extensive range of genotoxicity tests ranging from mutational assays in bacteria (e.g. Ames test), mutation and chromosome damage tests on mammalian cells in vitro, chromosome damage tests in mouse bone marrow and erythroid precursor cells exposed in vivo, and DNA damage assays in the nuclei of liver cells of rats exposed to omeprazole in vivo. The conclusions from these studies were uniformly negative. Details of the tests are summarized in this review.

Animals↗

PubMed1988

Monoclonal antibody ERY-1 identifies an antigen in erythroid cells, hepatocellular and renal cell carcinomas.

We have identified a monoclonal antibody (ERY-1), which reacts with erythrocytes, erythroid precursor cells, and with embryonal yolk sac, and normal liver and kidney. The antibody also decorates the neoplastic cells of hepatocellular, renal, and yolk sac carcinomas. No reactivity was seen in a variety of other epithelial or mesenchymal neoplasms. It is possible that ERY-1 recognizes an erythropoiesis-associated antigen present in yolk sac, kidney, liver, and bone marrow, all of which are involved in erythropoiesis in various stages of human development. Furthermore, ERY-1 has proved to be extremely useful in the histopathologic diagnosis of hepatocellular and renal cell carcinomas.

Antibodies, Monoclonal↗

PubMed1988

Effects of an aplastic anemia urinary extract on mouse erythroid progenitor cells in vivo.

We investigated the in vivo effects of a crude extract from the urine of aplastic anemia patients (AA urinary extract) on erythroid precursor cells in the femoral bone marrow and spleens of normal adult mice. A single intraperitoneal injection of AA urinary extract induced a significant increase in the number of splenic erythroid burst-forming units (BFU-e) and erythroid colony-forming units (CFU-e) within 24 h after injection. We then injected pure recombinant erythropoietin (Epo) equivalent to the amount present in the urinary extract. This addition increased the number of splenic CFU-e by almost the same degree as the amount induced by the AA urinary extract 24 h after injection, but failed to elicit any change in the number of splenic BFU-e. In other studies, mice were injected with the same amount of lipopolysaccharide (LPS) and/or pure Epo as that present in the AA urinary extract. Experiments with Limulus amebocyte lysate-adsorbed (endotoxin-depleted) or nonadsorbed (endotoxin-containing) AA urinary extracts showed that endotoxin contamination interfered with the increase in numbers of marrow CFU-e and enhanced the increase in splenic CFU-e numbers induced by pure Epo or Epo activity in the AA urinary extract. The number of splenic BFU-e, however, was not affected by administration of LPS and/or Epo or by adsorbed endotoxin. These data suggest that AA urinary extract contains a stimulating activity for mouse splenic BFU-e, and that this activity is not attributable to the Epo activity or endotoxin contamination within the urinary extract.

Adsorption↗

PubMed2000

Erythropoietic reconstitution, macrophages and reticulin fibrosis in bone marrow specimens of CML patients following allogeneic transplantation.

A clinicopathological study was conducted on 351 bone marrow trephine biopsies derived from 124 patients with chronic myeloid leukemia (CML) at standardized endpoints before and after allogeneic bone marrow transplantation (BMT). The purpose was to investigate quantitative changes of the nucleated erythroid precursor cell population and other associated features such as resident bone marrow macrophages and myelofibrosis and to elucidate their relevance on engraftment parameters. Monoclonal antibodies were applied for the identification of erythroid precursors and the labeling of mature macrophages; argyrophilic (reticulin-collagen) fibers were demonstrated by a silver impregnation technique. Following morphometric analysis of the pregraft bone marrow specimens statistical evaluation was in line with an adverse correlation between early to moderate reticulin fibrosis and amount of erythropoiesis. Moreover, a significant relationship was calculable between numbers of erythroid precursors and CD68+ macrophages. After myelo-ablative therapy and BMT a pronounced decrease in cellularity and in the quantity of erythropoiesis was found. Comparable with the pregraft samples, a significant association between erythroid precursors and macrophages could be determined in the regenerating donor bone marrow. A pretransplant relevant reduction of the red cell lineage and a manifest (reticulin) myelofibrosis indicating an advanced stage of disease were accompanied by a significant delay to reach transfusion independence. This result was further supported by comparable findings in trephine biopsies performed in the early post-transplant period (second month after BMT). Corresponding examinations revealed an enhancement of fiber density and a decrease in erythropoiesis in those patients who did not conform with the usually accepted criteria for successful engraftment. In conclusion, compelling evidence has been produced that a significantly reduced amount of erythroid precursors, which is usually associated with myelofibrosis in the pretransplant bone marrow, exerts an impairment to undisturbed hematopoietic reconstitution. Moreover, a close spatial and numerical relationship between the erythroid lineage and resident (mature) macrophages is observable, in particular in the state of regeneration after BMT.

Adolescent↗

PubMed1997

Presence of a functional vitamin D receptor does not correlate with vitamin D3 phenotypic effects in myeloid differentiation.

Although VDR is expressed in all the acute myeloid leukemia cell populations studied, most of these leukemias do not exhibit any phenotypic response when exposed to VD. To determine whether VD resistance is related to an altered VDR function, we performed an analysis of VDR expression, phosphorylation, DNA binding capacity and transactivation activity in several leukemic myeloid cell lines arrested at different levels of maturation. Our results indicate that VD induces a clear phenotypic effect, i.e. terminal monocytic differentiation, only in leukemic cells of M2/M3 (intermediate myeloblasts) and M5 (monoblasts) types but not in erythroid precursor cells, early leukemic myeloblasts (M0/M1 type) and promyelocytes (M3 type). VDR expression and function are evident in all the nuclear extracts obtained from the different myeloid cell lines after 12 h of VD treatment, but VD activation of monocytic differentiation is limited to a narrow differentiation window characterized by the M2 type myeloid cellular context.

Journal Article↗

PubMed2004

Phenotypic expression of pyruvate kinase deficiency and protection against malaria in a mouse model.

The recombinant congenic mouse strains AcB55 and AcB61 are extremely resistant to malaria (Plasmodium chabaudi AS) despite the presence of susceptibility alleles at the known Char1/Char2 resistance loci. Resistance in AcB55 and AcB61 is controlled by a locus on chromosome 3 (Char4) shown to be allelic with or tightly linked to a loss-of-function mutation in pyruvate kinase (Pklr). AcB55 and AcB61 show important splenomegaly prior to infection caused by the expansion of the red pulp, and display histological signs of extramedullary erythropoiesis in the liver. Examination of splenic cell populations by flow cytometry demonstrates elevated numbers of TER119-positive erythroid precursor cells (>30% of total spleen cells), while RNA expression studies show elevated expression of erythrocyte-specific transcripts such as globin, transferrin receptor, and Nramp2/Slc11a2 in the spleen of both strains. Hematological profiling in both strains is consistent with the presence of anemia as evidenced by low total erythrocyte counts, decreased hemoglobin, as well as abnormally high numbers of circulating reticulocytes (15-20%). These results strongly suggest that the mutant Pklr allele (Pklr(269A)) of AcB55/61 strains causes hemolytic anemia compensated by constitutive erythropoiesis, which in turn protects the mice against P. chabaudi infection. The possible molecular basis of the Pklr protective effect is discussed and is under current investigation in these two strains.

Anemia, Hemolytic↗

PubMedDate not supplied

[Expression of the membrane antigens in native and cryopreserved embryonic precursor cells].

Native and cryoconservated human embryonic liver cells at different stages of gestation (5, 6 and 7 weeks) have been studied. Tissue desagregation was performed by trypsinisation technique. A part of the samples was studied after their trypsinisation, another part - after 3-week storage. Cell viability of all samples was higher than 90%. CD34 antigen expression was highest in 5-week gestation samples. The tendency of the deacrease of CD34 antigen expression was seen in 7-week gestation samples. CD34 antigen expression was higher in the samples after their cryoconservation than in native ones. The CD34 antigen expression afer their cryoconservation was accompanied by an increase in numbers of cells expressing CD38, CD45RA, CD33, CD13 and CD14 antigens as well as markers of erythroid precursor cells -CD71, CD36 and CD45RO. Percentage of alpha-actin positive cells was higher in 6- and 7-week samples. An increase in alpha-actin positive cell fraction has been seen also in samples after their cryogenic conservation.

Antigens, CD↗

PubMed1993

Erythropoiesis in CML--immunomorphometric quantification, PCNA-reactivity, and influence on survival.

An immunohistochemical and morphometric analysis was performed on trephine biopsy specimens in 60 patients with chronic myeloid leukemia (CML) to quantify erythropoiesis and its proliferation capacity and to assess the stainable marrow iron (hemosiderin). For this purpose, an elaborate double-immunostaining technique was applied. This included a monoclonal antibody (PC10) that is directed against proliferating cell nuclear antigen (PCNA), followed by an antibody against glycophorin C (Ret40f), to identify all nucleated erythroid precursor cells. Additionally, morphometric data were derived from immunostaining of megakaryocytes (CD61) and macrophages (PG-M1), including its hemosiderin-laden subpopulation. Finally the determination of argyrophilic (reticulin) fiber density was carried out. In comparison with a control group (15 patients) without any hematologic disorder, in CML patients morphometric evaluation showed a significant reduction in the number of erythroblasts and normoblasts. This feature was associated with a PCNA-labeling index within the normal range and a decreased stainable marrow iron (number of hemosiderin-storaging macrophages). Several parameters were established to exert a predictive value on survival. A worsening of prognosis was associated with a decrease in the number of erythroid precursors (< 460/mm2), a low hemoglobin level (< 10 g/dl), a high megakaryocyte count (> 50 cells/mm2), an increased density of reticulin fibers (> 30 i x 10(2)/mm2) and splenomegaly (> 15 cm below costal margin). Our findings are in keeping with results obtained from in vitro studies of cell proliferation in CML, which is not significantly altered in comparison with the normal bone marrow. Finally, the present data, although derived from a small group of patients, emphasize the impact of histologic variables to be included in one of the major clinical trials on prognosis in CML.

Bone Marrow↗

PubMed2002

Apoptotic activity in villous trophoblast cells during B19 infection correlates with clinical outcome: assessment by the caspase-related M30 Cytodeath antibody.

Human parvovirus B19 (B19) infection during pregnancy can result in horizontal transmission of the virus and congenital infection. The main targets for B19 replication are the erythroid precursor cell of the colony and burst forming units. The cellular receptor necessary for B19 infectivity is globoside. Other non-erythroid cells can express this receptor, including megakaryocytes, endothelial cells, cardiac myocytes and placental trophoblast cells. B19 infection of globoside-containing erythroid cells results in cell death via apoptosis. We asked whether globoside-containing placental trophoblast cells, although not permissive for complete viral replication, would show evidence of apoptotic activity as a result of B19 infection. Placentas from 26 pregnancies with documented maternal and/or congenital B19 infection, 14 with poor outcomes and 12 with good outcomes were examined for evidence of apoptosis using the caspase-related M30 Cytodeath monoclonal antibody (Mab). M30 Mab recognizes a caspase 3 directed cleavage event within cytokeratin 18, a protein widely distributed in epithelial cells, of which trophoblast cells are classified. The results of the immunohistochemical analysis revealed a significant number of M30-staining placental villous trophoblast cells from B19-complicated pregnancies with poor outcomes compared to B19-complicated pregnancies with good outcomes or the 24 age-matched controls (P< 0.001). This is the first description of an association between B19-complicated pregnancies ending in foetal death and increased apoptosis within placental villous trophoblast cells. Damage due to premature death of the protective barrier of the placental trophoblast layer may compromise its integrity and play a role in pathogenesis.

Antibodies, Monoclonal↗

PubMed1991

Lymphocyte-selective cytostatic and immunosuppressive effects of mycophenolic acid in vitro: role of deoxyguanosine nucleotide depletion.

Mycophenolic acid (MPA), an inhibitor of inosine monophosphate dehydrogenase, in nanomolar concentrations blocks proliferative responses of cultured human, mouse and rat T lymphocytes and B lymphocytes to mitogens or in mixed lymphocyte reactions. The inhibitory effect of MPA on lymphocyte proliferation is reversed by addition to culture media of deoxyguanosine or guanosine but not by addition of deoxyadenosine or adenosine. The findings suggest that the principal mechanism of action of low concentrations of MPA is depletion of deoxyguanosine triphosphate which is required for DNA synthesis. In immunosuppressive doses, MPA does not affect the formation of IL-1 by LPS-activated human peripheral blood monocytes. Unlike cyclosporin A and FK-506, MPA does not inhibit the formation of IL-2 and the expression of the IL-2 receptor in mitogen-activated human T lymphocytes. MPA suppresses mixed lymphocyte reactions when added 3 days after their initiation. These findings suggest that MPA does not inhibit early responses of T and B lymphocytes to mitogenic or antigenic stimulation but blocks the cells at the time of DNA synthesis. The cytostatic effect of MPA is more potent on lymphocytes than on other cell types, such as fibroblasts and endothelial cells. MPA also inhibits antibody formation by polyclonally activated human B lymphocytes. MPA is an immunosuppressive agent reversibly inhibiting proliferation of T and B lymphocytes and antibody formation, with a profile of activity different from that of other immunosuppressive drugs. Human T and B lymphocytic and promonocytic cell lines are highly sensitive to the antiproliferative effects of MPA, whereas the erythroid precursor cell line K562 is less susceptible. The effect of MPA on cells of the monocyte-macrophage lineage could exert long-acting anti-inflammatory activity. MPA or analogues may have therapeutic utility in diseases such as rheumatoid arthritis, for prevention of allograft rejection and in lymphocytic or monocytic leukaemias and lymphomas.

Animals↗