Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MACROPHAGES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources
PubMed1999

Modulation of inducible nitric oxide synthase induction by prostaglandin E2 in macrophages: distinct susceptibility in murine J774 and RAW 264.7 macrophages.

Prostaglandin E2 (PGE2) is the major cyclooxygenase metabolite in macrophages with complex proinflammatory and immunoregulatory properties. In the present study, we have compared the modulatory role of PGE2/cAMP-dependent signaling on induced nitric oxide (NO) production in two murine macrophages, J774 and RAW 264.7. With no effect on NO release by itself, PGE2 co-addition with lipopolysaccharide (LPS) resulted in a concentration-dependent enhancement in NO release and inducible NO synthase induction in J774, but not in RAW 264.7, macrophages. The potentiation effect of PGE2 in J774 cells was still seen when applied within 9 h after LPS treatment. Whereas RAW 264.7 macrophages release PGE2 with greater extent than J774 macrophages in response to LPS, indomethacin and NS-398, upon abolishing LPS-induced PGE2 release, caused a more obvious inhibition of NO release from J774 than RAW 264.7 cells. Thus, we suggest a higher positive modulatory role of PGE2--either endogenous or exogenous--on NO formation in J774 cells. Supporting these findings, exogenous PGE2 triggers cAMP formation in J774 cells with higher potency and efficacy. Of interest, dBcAMP also elicits higher sensitivity in potentiating NO release in J774 cells. We conclude that the opposite effect of PGE2/cAMP signaling on macrophage NO induction depends on its signaling efficacy and might be associated with the difference in endogenous PGE2 levels.

Animals↗
PubMed1997

Effect of porcine reproductive and respiratory syndrome virus (PRRSV) (isolate ATCC VR-2385) infection on bactericidal activity of porcine pulmonary intravascular macrophages (PIMs): in vitro comparisons with pulmonary alveolar macrophages (PAMs).

Porcine pulmonary intravascular macrophages (PIMs) were recovered by in situ pulmonary vascular perfusion with 0.025% collagenase in saline from six 8-week old, crossbred pigs. Pulmonary alveolar macrophages (PAMs) were recovered by bronchoalveolar lavage from the same pigs for comparisons in each assay. The macrophages were exposed to PRRSV (ATCC VR-2385) in vitro for 24 h and infection was confirmed by an indirect immunofluorescence test or transmission electron microscopy. Viral particles tended to accumulate in the vesicles of the Golgi apparatus or endoplasmic reticulum. Bactericidal function assays were performed on the recovered macrophages to determine the effects of the virus on macrophage functions. In vitro PRRSV infection reduced the bactericidal ability of PIMs from 68.3% to 56.4% (P < 0.09), and PAMs from 69.3% to 61.0% (P > 0.1) at 24 h post-infection. The mean percentage of bacteria killed by macrophages after PRRSV infection was not significantly different among the treatment groups or between the treatment groups and non-infected controls based on colorimetric MTT bactericidal (Staphylococcus aureus) assay. PRRSV did not affect the ability of PIMs or PAMs to internalize opsonized 125I-iododeoxyuridine-labeled S. aureus (P > 0.05). PRRSV infection significantly decreased the production of superoxide anion (P < 0.01) by 67.0% in PIMs and by 69.4% in PAMs. PRRSV reduced the myeloperoxidase-H2O2-halide product (P < 0.01) by 36.5% for PIMs and by 48.1% for PAMs. The results suggest: (1) PIMs should be considered as an important replication site of PRRSV; (2) PRRSV may have a detrimental effect on both PIMs and PAMs; (3) loss of bactericidal function in PIMs may facilitate hematogenous bacterial infections.

Animals↗
PubMed1999

The effect of testicular macrophages, macrophage-conditioned medium and interleukin-1alpha on the cytoskeleton of bank vole Leydig cells.

Recently, morphological and functional interactions between cytoskeletal elements and their involvement in cell movements, shape changes and/or translocation of organelles have been intensively studied. Thus, the aim of our work was to determine whether testicular macrophages and/or their products have an influence on Leydig cell cytoskeleton. The source of Leydig cells and macrophages were male bank voles from spring and autumn generations, reared in different regime of light for 7-8 weeks. The Leydig cells were growing in monocultures or in co-cultures with testicular macrophages. All cell cultures were divided to controls or human chorionic gonadotropin-stimulated ones. To some of the cultures testicular macrophage-conditioned medium or interleukin-1alpha were added. The cells were analysed immunocytochemically and radioimmunologically. In Leydig cells obtained from animals kept in a long day, grown in co-cultures with macrophages as well as in those stimulated by testicular macrophage-conditioned medium, distinct rearrangements of microtubules and microfilaments were observed. This phenomenon was strengthened in the presence of hCG in culture media. Concomitantly, basal and hCG-stimulated level of testosterone was enhanced, which indicates the possible involvement of the cytoskeleton in the process of androgen biosynthesis. The influence of IL-1alpha on reorganization of cytoskeletal structures was not observed, suggesting that in the modulation of steroidogenesis by this cytokine cytoskeletal elements do not play an important role.

Animals↗
PubMed1978

Modulation of macrophage tumoricidal capability by polyene antibiotics: support for membrane lipid as a regulatory determinant of macrophage function.

We have examined the effects of the sterol-binding polyene antibiotics on macrophage tumoricidal capability. Incubation for 2 hr of activated macrophages from bacillus Calmette-Guérin-infected mice with amphotericin B at 0.5--2 microgram/ml or amphotericin B methyl ester at 0.5--10 microgram/ml enhanced the capability of activated macrophages to kill 3T12 cells. These polyenes did not make normal or stimulated macrophages tumoricidal. Experiments with the ionophores gramicidin, alamethecin, nigericin, and valinomycin indicate that the ionophoretic properties of amphotericin B may not account for its enhancing effect on macrophage tumoricidal potential. Two polyenes with a smaller ring structure, filipin and pimaricin, were also ineffective suggesting that stereospecific modifications in membrane lipid organization underlie the enhancing effect of amphotericin B. The results suggest that the clinical efficacy of amphotericin B in promoting resistance to fungal disease and possibly to neoplasia may operate in part through potentiation of macrophage effector functions.

Amphotericin B↗
PubMed1999

Receptors for oxidized low-density lipoprotein on elicited mouse peritoneal macrophages can recognize both the modified lipid moieties and the modified protein moieties: implications with respect to macrophage recognition of apoptotic cells.

It has been shown previously that the binding of oxidized low-density lipoprotein (OxLDL) to resident mouse peritoneal macrophages can be inhibited (up to 70%) by the apoprotein B (apoB) isolated from OxLDL, suggesting that macrophage recognition of OxLDL is primarily dependent on its modified protein moiety. However, recent experiments have demonstrated that the lipids isolated from OxLDL and reconstituted into a microemulsion can also strongly inhibit uptake of OxLDL (up to 80%). The present studies show that lipid microemulsions prepared from OxLDL bind to thioglycollate-elicited macrophages at 4 degrees C in a saturable fashion and inhibit the binding of intact OxLDL and also of the apoB from OxLDL. Reciprocally, the binding of the OxLDL-lipid microemulsions was strongly inhibited by intact OxLDL. A conjugate of synthetic 1-palmitoyl 2(5-oxovaleroyl) phosphatidylcholine (an oxidation product of 1-palmitoyl 2-arachidonoyl phosphatidylcholine) with serum albumin, shown previously to inhibit macrophage binding of intact OxLDL, also inhibited the binding of both the apoprotein and the lipid microemulsions prepared from OxLDL. Finally, a monoclonal antibody against oxidized phospholipids, one that inhibits binding of intact OxLDL to macrophages, also inhibited the binding of both the resolubilized apoB and the lipid microemulsions prepared from OxLDL. These studies support the conclusions that: (i) at least some of the macrophage receptors for oxidized LDL can recognize both the lipid and the protein moieties; and (ii) oxidized phospholipids, in the lipid phase of the lipoprotein and/or covalently linked to the apoB of OxLDL, likely play a role in that recognition.

Animals↗
PubMed2002

Activation of the RON receptor tyrosine kinase by macrophage-stimulating protein inhibits inducible cyclooxygenase-2 expression in murine macrophages.

The RON receptor tyrosine kinase is activated by macrophage-stimulating protein, which regulates macrophage migration, phagocytosis, and nitric oxide production. We report here the inhibitory effect of RON on lipopolysaccharide (LPS)-induced cyclooxygenase (Cox)-2 expression in mouse macrophages. In RON-expressing macrophages treated with macrophage stimulating protein, LPS-induced prostaglandin E(2) (PGE(2)) production was significantly reduced. The inhibition was accompanied by reduction of Cox-2 protein and mRNA expression. Transcriptional studies indicated that RON activation inhibits LPS-induced luciferase activity driven by the Cox-2 gene promoter. To determine whether RON activation affects LPS-induced NF-kappa B pathway, which is important for Cox-2 expression. Western blot analyses were performed showing that RON activation inhibits LPS-induced I kappa B alpha degradation. The decreased I kappa B alpha degradation was due to reduced I kappa B alpha phosphorylation at Ser-32 as determined by I kappa B alpha (Ser-32) phosphor-antibody. Moreover, we found that LPS-induced IKK beta activity, an enzyme responsible for phosphorylation of I kappa B alpha, was inhibited upon RON activation. Interestingly, these inhibitory effects were not regulated by RON-mediated phosphatidylinositol-3 kinase. These results suggest that RON activation inhibits LPS-induced macrophage Cox-2 expression. The inhibitory effect is mediated by impairing LPS-activated cascade enzymes that activate NF-kappa B. The inhibition of Cox-2 expression might represent a novel mechanism for the inhibitory functions of RON in vivo against LPS-induced inflammation and septic shock.

Androstadienes↗
PubMedDate not supplied

Reaction of macrophages to cigarette smoke. II. Immigration of macrophages to the lungs.

The present study identifies the source of the elevated pulmonary macrophage population in young adult male mice which results when animals are exposed to cigarette smoke. Light microscopic and autoradiographic analysis of pulmonary tissue from smoke-exposed animals revealed that pulmonary macrophages (free, attached, and septal or interstitial) divide only rarely. Further, it was noted that, during the marked progressive increase in the labeled macrophage population in the lungs, the number of silver grains over the nuclei of labeled macrophages did not become significantly diluted. Thus, the markedly elevated macrophage population which results when animals are exposed to cigarette smoke appears, for the most part, to be due to immigration of cells from bone marrow rather than in situ division of resident macrophages.

Animals↗
PubMed1988

Macrophage interactions with laminin: PMA selectively induces the adherence and spreading of mouse macrophages on a laminin substratum.

The ability of thioglycollate (TG)-elicited mouse peritoneal macrophages to adhere to a laminin substratum has been studied. These cells do not adhere to laminin-coated (20 micrograms/ml) surfaces, but the addition of phorbol myristate acetate (PMA; 50 ng/ml) results in their rapid adherence and spreading on this substratum. TG-elicited and PMA-activated macrophages, however, can bind soluble laminin. Macrophages adhere to fibronectin-coated surfaces and tissue culture plastic without PMA stimulation, and PMA does not increase the number of cells that adhere to these surfaces. The predominant surface proteins that bind specifically to laminin-Sepharose exhibit an Mr of 67 and 36 kD, but the expression of these proteins does not increase after PMA stimulation. Laminin receptor antibodies immunoprecipitate the 67-kD protein from radiolabled surface lysates and are capable of blocking macrophage adherence to a laminin substratum. Indirect immunofluorescence microscopy indicates that PMA stimulation does not increase receptor expression, but that it may induce the aggregation of the receptor on the cell surface. PMA stimulation also promotes macrophage spreading and induces a reorganization of the actin cytoskeleton. Taken together, these data indicate the mechanism by which PMA promotes macrophage adherence to laminin does not involve increased 67-kD receptor surface expression, but that it is related to the changes in cytoskeletal and receptor surface organization that occur in response to PMA stimulation.

Animals↗
PubMed1972

Phagocytosis of immune complexes by macrophages. Different roles of the macrophage receptor sites for complement (C3) and for immunoglobulin (IgG).

Sheep red cells (E) sensitized with IgG antibody (EA) or with antibody and complement (EAC) interact in vitro with mouse peritoneal macrophage monolayers. The role of IgG and of C3 in the attachment and ingestion of the erythrocytes was examined by means of quantitative technique utilizing (51)Cr-labeled E. Controlled osmotic lysis permitted the separate measurement of the radioactivity associated with bound or with ingested E. IgG-(125)I was used to estimate the number of IgG molecules bound per E as a function of the IgG concentration. Control experiments showed that iodination did not influence the extent of binding of IgG to E and that the binding of IgG prepared from immune serum could be essentially ascribed to its anti-E antibody content. Only between 10(3) and 10(4) rabbit anti-E IgG molecules per erythrocyte were needed for detectable attachment and ingestion of EA (a maximum number of 6 x 10(5) IgG antibody molecules could be accomodated on one erythrocyte). Evidence was obtained that C3 is primarily involved in particle attachment, whereas only IgG is able to markedly promote the ingestion of particles attached to macrophages: (a) Addition of complement to the EA substantially increased the binding to the macrophages, whereas ingestion was increased to a smaller extent. Both binding and ingestion of EAC were markedly inhibited by papain fragments of IgG obtained from a rabbit antiserum to mouse C3. (b) Low doses (2 microg/ml) of papain fragments of IgG from a rabbit antiserum to mouse IgG markedly reduced the ingestion of EAC, whereas attachment of EAC to macrophages was inhibited to a much smaller degree. The possible relevance of these findings for the in vivo fate of particulate immune complexes as they interact with macrophages is discussed. It is suggested that in the primary immune response, when the complexes are predominantly in the form of EA (IgM) or EA (IgM) C3, they would tend to remain on the surface of the macrophages and thus be in a position to stimulate immunocompetent cells. In the secondary response, when EA (IgG) or EA (IgG) C3 predominate, the complexes would tend to be more rapidly interiorized and degraded by the mononuclear phagocytes,

Animals↗
PubMed1979

Studies on the mechanisms of macrophage activation. II. Parasite destruction in macrophages activated by supernates from concanavalin A-stimulated lymphocytes.

Activation of mouse peritoneal exudate macrophages, as evidenced by destruction of the intracellular protozoan parasite Leishmania enriettii, was obtained by incubation with supernates from concanavalin A (Con A)-stimulated syngeneic spleen cells. Parasites were not destroyed in macrophages exposed to control media. Supernate-induced activation was independent of the presence of Con A. The activating principle (macrophage activating factor, or MAF) was produced by Con A-stimulated lymphocytes in presence or absence of serum. In absence of serum, MAF synthesis was highest at Con A concentrations far below those required in serum-containing media. MAF production was reduced at Con A concentrations of 10 microgram/ml or above, probably a result of toxicity of the lectin for lymphocytes. MAF was detectable after 24 h of lymphocyte stimulation and increased up to 72 h; production appeared to be independent of DNA synthesis. Serum-free MAF was inactive when tested as such on macrophages. Full activity could be restored by addition of nanogram amounts of endotoxin or of FCS before assay. Endotoxin also considerably potentiated MAF activity in serum-containing supernates. Full intracellular parasite destruction was observed after contact of macrophages with MAF for 20 h. The continuous presence of MAF was not necessary for activation; a 10-h pulse was sufficient to induce macrophages to destroy all intracellular microorganisms within the next 38 h.

Animals↗
PubMed1980

Role of I-region gene products in macrophage induction of an antibody response. II. Restriction at the level of T cell in recognition of I-J-subregion macrophage determinants.

The effect of specific anti-I-J reagents on macrophage-T cell interactions was studied in an in vitro antibody response to burro erythrocytes. Macrophages were prepared from the spleens of F1 hybrid mice whose parental strains differed at the I-J subregion. Two F1 hybrids were used for these experiments, [B10.A(3R) X B10.A(5R)]F1 and [B10.S(9R) X B10.HTT]F1. F1 macrophages responded equally well with F1 T-B cells or with T-B cells of either parental strain. When F1 macrophages were pretreated with anti-I-J serum (without complement) specific for one parental haplotype, they were only able to cooperate with T helper (TH) cells of the unblocked haplotype and with F1 TH cells. Identical results were obtained with (Jb X Jk)F1 and (Js X Jk)F1 mice. The results indicate that TH cells possess genetically restricted receptors for macrophage I-J-subregion gene products and that the interaction between this receptor and the macrophage I-J-subregion determinants is essential for the initiation of a primary in vitro antibody response to an erythrocyte antigen.

Animals↗
PubMed1996

The interaction of macrophage and non-macrophage tropic isolates of HIV-1 with thymic and tonsillar dendritic cells in vitro.

Dendritic cells isolated from thymus and tonsil were tested for susceptibility to HIV-1 strains that are tropic for macrophages or for T cell lines. DCs were purified by cell sorting and before infection expressed high levels of CD4 and HLA-DR and lacked markers for T, B, NK cells, or macrophages. Viral entry and reverse transcription was found after pulsing with strains of HIV-1 that could infect macrophages. During the first 36 h the PCR signals for gag sequences increased in DCs and macrophages. In contrast little if any viral DNA was found after pulsing macrophages or DCs with HIV-1 that was able to infect T cell lines. DCs pulsed with HIV-1 were able to transmit infection to responding T cells during an allogeneic or superantigen response. Selection for virus able to infect lymphoid DCs and other DCs expressing CD4 and its transfer to T cells during subsequent immune responses may provide a mechanism for the observed predominance of macrophage-tropic HIV-1 after in vivo transmission.

CD4 Antigens↗
PubMed1999

Adoptive transfer of genetically modified macrophages elucidated TGF-beta-mediated 'self-defence' of the glomerulus against local action of macrophages.

TGF-beta has several anti-inflammatory properties which may be relevant to prevention of or recovery from acute glomerular inflammation. Using genetically modified mesangial cells and a technique for in vivo macrophage transfer, this article provides evidence for TGF-beta-mediated 'self-defence' of the glomerulus against macrophages. Rat mesangial cells stably transfected with TGF-beta1 showed a blunted response to the macrophage-derived, proinflammatory cytokine IL-1beta. In contrast, mesangial cells expressing the dominant-interfering TGF-beta receptor showed an enhanced response to IL-1. Similarly, externally added TGF-beta1 inhibited the cytokine response of normal glomeruli, and isolated nephritic glomeruli producing active TGF-beta1 showed a depressed response to IL-1beta, compared to normal glomeruli. Consistent with these in vitro results, in vivo transfer of activated macrophages revealed that the TGF-beta-producing glomeruli are insensitive to the effector action of macrophages. These results indicate that TGF-beta1 functions as an endogenous 'defender' that counteracts local action of activated macrophages in the glomerulus.

Adoptive Transfer↗
PubMed1996

Effects of calcium on the migration and recruitment of macrophages and macrophage-derived foam cells.

Calcium is thought to play an important role in the genesis of atherosclerotic lesions, but the precise mechanisms involved are unclear. In the present investigation, we have used in vitro systems to investigate the effects of calcium on one key aspect of lesion development: the migration of macrophages and macrophage/foam cells. Using agarose plate migration assays, the migratory characteristics of macrophages exposed to 1) no lipoprotein, 2) low density lipoprotein (LDL), 3) acetylated low density lipoprotein (acLDL), and ) oxidized low density lipoprotein were examined. The most marked stimulatory effect on macrophage mobility was observed when freshly isolated cells were exposed to acLDL during the migration assay. High levels of exogenous calcium were found to suppress the stimulatory effect of acLDL on migration. As the responses of macrophages exposed to a uniform concentration of agents in the surrounding medium may differ from chemotactic responses to a concentration gradient, the migration of macrophages, with and without preexposure to acLDL or LDL, was studied using microchemotaxis Boyden chambers. Under these conditions, calcium acted as a highly potent chemoattractant, especially to cells that had been preincubated with acLDL. These results suggest how elevated external calcium concentration leads initially to macrophage recruitment, and subsequently to foam cell aggregation and lipid core formation, in association with calcification, in the developing atherosclerotic plaque.

Animals↗
PubMed2005

Immunosenescence and macrophage functional plasticity: dysregulation of macrophage function by age-associated microenvironmental changes.

The macrophage lineage displays extreme functional and phenotypic heterogeneity, which appears to be because, in large part, of the ability of macrophages to functionally adapt to changes in their tissue microenvironment. This functional plasticity of macrophages plays a critical role in their ability to respond to tissue damage and/or infection and to contribute to clearance of damaged tissue and invading microorganisms, to recruitment of the adaptive immune system, and to resolution of the wound and of the immune response. Evidence has accumulated that environmental influences, such as stromal function and imbalances in hormones and cytokines, contribute significantly to the dysfunction of the adaptive immune system. The innate immune system also appears to be dysfunctional in aged animals and humans. In this review, the hypothesis is presented and discussed that the observed age-associated 'dysfunction' of macrophages is the result of their functional adaptation to the age-associated changes in tissue environments. The resultant loss of orchestration of the manifold functional capabilities of macrophages would undermine the efficacy of both the innate and adaptive immune systems. The macrophages appear to maintain functional plasticity during this dysregulation, making them a prime target of cytokine therapy that could enhance both innate and adaptive immune systems.

Aging↗
PubMed1980

Recognition of heterologous cells by macrophages. II. The mechanism of phagocytosis of chicken thymocytes by mouse and guinea pig macrophages.

Mouse and guinea pig macrophages cultured in vitro actively phagocytize non-opsonized thymocytes from certain heterologous animals including chickens, as shown in the accompanying paper (11). The present study was undertaken to investigate the mechanism of this phenomenon, using the phagocytosis of chicken thymocytes (c-thymocytes) by mouse and guinea pig macrophages. The involvement in this phenomenon of natural IgG passively adsorbed in situ to macrophages was excluded, since the phagocytosis of c-thymocytes was not significantly affected by the treatment of macrophages with homologous IgG or rabbit anti-sera directed toward homologous IgG. The involvement of lectin- or sugar-like receptors seems also to be unlikely, since various glycoproteins showed no significant effect. c-Thymocytes treated with normal mouse serum (NMS) but not with heat-inactivated NMS were strongly stained with goat anti-mouse C3 by an indirect immunofluorescent technique, and became extremely vulnerable to adherence to and phagocytosis by mouse macrophages, suggesting that c-thymocytes are an activator of the alternative pathway of mouse complement. These results as a whole raise the possibility that mouse and guinea pig macrophages can phagocytize c-thymocytes by recognizing their activating surfaces of the alternative complement pathway without the participation of exogenously added IgG or complement, as proposed by others in the phagocytosis of rabbit and mouse red blood cells by human monocytes.

Animals↗
PubMed1980

Complement proteins and macrophages. II. The secretion of factor B by lipopolysaccharide-stimulated macrophages.

The secretion of factor B by mouse peritoneal macrophages was found to be enhanced following in vivo or in vitro stimulation with lipopolysaccharide (LPS). The intravenous administration of LPS to mice of various strains caused an increased release of factor B but not the release of acid phosphatase by the peritoneal macrophages obtained from the stimulated mice. In vitro stimulation of cultured macrophages with LPS resulted in an enhanced secretion of both factor B and acid phosphatase. The dose-dependent augmentation of factor B secretion by LPS was found in the macrophages from LPS-responsive C3H/HeN mice, whereas the macrophages from LPS-unresponsive C3H/HeJ mice did not respond to either phenol-extracted LPS or butanol-extracted LPS. The ability of LPS to cause the enhancement of factor B secretion by macrophages was abolished by alkali or acid treatment of LPS, indicating that its lipid A part was responsible for the observed effect.

Acetates↗
PubMed1987

Evidence of drug metabolism by macrophages: possible role of macrophages in the pathogenesis of drug-induced tissue damage and in the activation of environmental procarcinogens.

After interaction with human macrophages derived from blood, bone marrow or spleen, solutions of sodium phenobarbitone, phenytoin sodium and chlorpromazine hydrochloride showed reduced cytotoxicity towards K562 cells. The reduction in cytotoxicity was partially suppressed in the presence of tetrahydrofurane, an inhibitor of cytochrome P450. These data suggest that macrophages are capable of metabolizing certain drugs, probably via a cytochrome P450-dependent mechanism. The present findings raise the possibility that some drug-induced blood dyscrasias are caused by metabolism of the drug by bone marrow macrophages and the consequent release of relatively short-lived molecules which are toxic to adjacent haemopoietic cells. The generation of cytotoxic molecules during drug metabolism by macrophages may also be responsible for drug-induced damage to other macrophage-rich tissues. In addition, since cytochrome P450-dependent reactions seem to occur within macrophages, these cells may activate environmental procarcinogens and thus plays a role in carcinogenesis and leukaemogenesis.

Cells↗