Bisphosphonates (BPs) are compounds resembling the pyrophosphate structure. BPs bind the mineral component of bones. During the bone resorption by osteoclasts, nitrogen-containing BPs are released and internalized, causing an inhibition of the mevalonate pathway. As a consequence, osteoclasts are unable to execute their function. Alendronate (ALN) is a bisphosphonate used to treat osteoporosis. Its administration could be associated with adverse effects. The purpose of this study is to evaluate four different ALN concentrations, ranging from 10-6 to 10-10 M, in the presence of different combinations of M-CSF and RANKL, to find out the effect of low ALN concentrations on osteoclastogenesis using rat and human peripheral blood mononuclear cells. The cytotoxic effect of ALN was evaluated based on metabolic activity and DNA concentration measurement. The alteration in osteoclastogenesis was assessed by the activity of carbonic anhydrase II (CA II), tartrate-resistant acid phosphatase staining, and actin ring formation. The ALN concentration of 10-6 M was cytotoxic. Low ALN concentrations of 10-8 and 10-10 M promoted proliferation, osteoclast-like cell formation, and CA II activity. The results indicated the induction of osteoclastogenesis with low ALN concentrations. However, when high doses of ALN were administered, their cytotoxic effect was demonstrated.

• Klíčová slova
• M-CSF, RANKL, alendronate, osteoclastogenesis,
• MeSH
• aktiny metabolismus   MeSH
• alendronát farmakologie   MeSH
• barvení a značení MeSH
• DNA metabolismus   MeSH
• faktor stimulující kolonie makrofágů farmakologie   MeSH
• karboanhydrasa II metabolismus   MeSH
• krysa rodu Rattus MeSH
• kyselá fosfatasa rezistentní k tartarátu metabolismus   MeSH
• leukocyty mononukleární účinky léků   metabolismus   MeSH
• lidé MeSH
• ligand RANK farmakologie   MeSH
• osteogeneze účinky léků   MeSH
• osteoklasty účinky léků   enzymologie   metabolismus   MeSH
• proliferace buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aktiny MeSH
• alendronát MeSH
• DNA MeSH
• faktor stimulující kolonie makrofágů MeSH
• karboanhydrasa II MeSH
• kyselá fosfatasa rezistentní k tartarátu MeSH
• ligand RANK MeSH

Bordetella pertussis infects the upper airways of humans and disarms host defense by the potent immuno-subversive activities of its pertussis (PT) and adenylate cyclase (CyaA) toxins. CyaA action near-instantly ablates the bactericidal activities of sentinel CR3-expressing myeloid phagocytes by hijacking cellular signaling pathways through the unregulated production of cAMP. Moreover, CyaA-elicited cAMP signaling also inhibits the macrophage colony-stimulating factor (M-CSF)-induced differentiation of incoming inflammatory monocytes into bactericidal macrophages. We show that CyaA/cAMP signaling via protein kinase A (PKA) downregulates the M-CSF-elicited expression of monocyte receptors for transferrin (CD71) and hemoglobin-haptoglobin (CD163), as well as the expression of heme oxygenase-1 (HO-1) involved in iron liberation from internalized heme. The impact of CyaA action on CD71 and CD163 levels in differentiating monocytes is largely alleviated by the histone deacetylase inhibitor trichostatin A (TSA), indicating that CyaA/cAMP signaling triggers epigenetic silencing of genes for micronutrient acquisition receptors. These results suggest a new mechanism by which B. pertussis evades host sentinel phagocytes to achieve proliferation on airway mucosa.IMPORTANCETo establish a productive infection of the nasopharyngeal mucosa and proliferate to sufficiently high numbers that trigger rhinitis and aerosol-mediated transmission, the pertussis agent Bordetella pertussis deploys several immunosuppressive protein toxins that compromise the sentinel functions of mucosa patrolling phagocytes. We show that cAMP signaling elicited by very low concentrations (22 pM) of Bordetella adenylate cyclase toxin downregulates the iron acquisition systems of CD14+ monocytes. The resulting iron deprivation of iron, a key micronutrient, then represents an additional aspect of CyaA toxin action involved in the inhibition of differentiation of monocytes into the enlarged bactericidal macrophage cells. This corroborates the newly discovered paradigm of host defense evasion mechanisms employed by bacterial pathogens, where manipulation of cellular cAMP levels blocks monocyte to macrophage transition and replenishment of exhausted phagocytes, thereby contributing to the formation of a safe niche for pathogen proliferation and dissemination.

• Klíčová slova
• Bordetella pertussis, adenylate cyclase toxin, cyclic AMP, differentiation, iron acquisition, macrophages, monocytes,
• MeSH
• adenylátcyklasový toxin * metabolismus   genetika   MeSH
• AMP cyklický * metabolismus   MeSH
• antigen CD163 MeSH
• antigeny diferenciační myelomonocytární MeSH
• Bordetella pertussis * MeSH
• buněčná diferenciace * MeSH
• CD antigeny metabolismus   genetika   MeSH
• lidé MeSH
• lipopolysacharidové receptory * metabolismus   MeSH
• monocyty * metabolismus   imunologie   mikrobiologie   MeSH
• proteinkinasy závislé na cyklickém AMP metabolismus   MeSH
• receptory buněčného povrchu metabolismus   genetika   MeSH
• signální transdukce * MeSH
• upregulace MeSH
• železo metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenylátcyklasový toxin * MeSH
• AMP cyklický * MeSH
• antigen CD163 MeSH
• antigeny diferenciační myelomonocytární MeSH
• CD antigeny MeSH
• CD14 protein, human MeSH Prohlížeč
• lipopolysacharidové receptory * MeSH
• proteinkinasy závislé na cyklickém AMP MeSH
• receptory buněčného povrchu MeSH
• železo MeSH

Macrophage colony-stimulating factor receptor (M-CSFR/CSF1R) signaling is crucial for the differentiation, proliferation, and survival of myeloid cells. The CSF1R pathway is a promising therapeutic target in many human diseases, including neurological disorders and cancer. Zebrafish are commonly used for human disease modeling and preclinical therapeutic screening. Therefore, it is necessary to understand the proper function of cytokine signaling in zebrafish to reliably model human-related diseases. Here, we investigate the roles of zebrafish Csf1rs and their ligands (Csf1a, Csf1b, and Il34) in embryonic and adult myelopoiesis. The proliferative effect of exogenous Csf1a on embryonic macrophages is connected to both receptors, Csf1ra and Csf1rb, however there is no evident effect of Csf1b in zebrafish embryonic myelopoiesis. Furthermore, we uncover an unknown role of Csf1rb in zebrafish granulopoiesis. Deregulation of Csf1rb signaling leads to failure in myeloid differentiation, resulting in neutropenia throughout the whole lifespan. Surprisingly, Il34 signaling through Csf1rb seems to be of high importance as both csf1rbΔ4bp-deficient and il34Δ5bp-deficient zebrafish larvae lack granulocytes. Our single-cell RNA sequencing analysis of adult whole kidney marrow (WKM) hematopoietic cells suggests that csf1rb is expressed mainly by blood and myeloid progenitors, and the expression of csf1ra and csf1rb is nonoverlapping. We point out differentially expressed genes important in hematopoietic cell differentiation and immune response in selected WKM populations. Our findings could improve the understanding of myeloid cell function and lead to the further study of CSF1R pathway deregulation in disease, mostly in cancerogenesis.

• MeSH
• dánio pruhované * genetika   MeSH
• hematopoéza MeSH
• ligandy MeSH
• receptor faktoru stimulujícího kolonie makrofágů * metabolismus   MeSH
• signální transdukce MeSH
• transportní proteiny metabolismus   MeSH
• tyrosinkinasové receptory metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ligandy MeSH
• receptor faktoru stimulujícího kolonie makrofágů * MeSH
• transportní proteiny MeSH
• tyrosinkinasové receptory MeSH

OBJECTIVE AND DESIGN: To determine whether nonadherent macrophage precursors are present within the inflamed peritoneal cavity in mice, we analysed the mononuclear cell populations from different peritoneal tissues. OBJECTS: A group of 90 female mice BDF1 (C57BL/ 6 x DBA/2) was used for the study. Mononuclear cells were harvested from the peripheral blood, bone marrow, peritoneal exudate, omentum, mesentery, parietal peritoneum and diaphragm. TREATMENT: Mice were injected intraperitoneally with 0.2 ml of Freund's incomplete adjuvant. Animals were sacrificed at 6, 13, 16, 21 and 30 days. Three to six animals were examined for each time period. METHODS: Progenitor cell assay was performed in 1 ml of semi-solid agarose (0.3% Seakem GTG) DMEM which was supplied either with recombinant colony stimulating factors or with mesothelial cell-conditioned medium. RESULTS: Nonadherent macrophage-colony forming cells were present in all peritoneal compartments (35-140 precursor cells/5 x 10(4) mononuclear cells). Granulocyte/ macrophage-colony forming cells were found in the inflamed omentum. Combined simultaneous treatment with GM-CSF and M-CSF blocked the proliferation of the exudate and mesentery-derived macrophage precursors, but not other peritoneal tissue-derived macrophage precursors. Sequential stimulation with GM-CSF and M-CSF did not inhibit macrophage colony formation. CONCLUSIONS: GM-CSF can possibly influence the proliferative response induced by M-CSF. Nonadherent macrophage precursors recovered from different tissue compartments seem to differ in their sensitivity to growth regulation.

• MeSH
• analýza kolonii tvořících jednotek MeSH
• ascitická tekutina metabolismus   MeSH
• buněčné dělení účinky léků   MeSH
• exsudáty a transsudáty metabolismus   MeSH
• faktor stimulující granulocyto-makrofágové kolonie toxicita   MeSH
• faktor stimulující kolonie makrofágů toxicita   MeSH
• fibronektiny metabolismus   MeSH
• Freundovo adjuvans aplikace a dávkování   toxicita   MeSH
• injekce intraperitoneální MeSH
• kmenové buňky cytologie   účinky léků   MeSH
• leukocyty mononukleární cytologie   účinky léků   patologie   MeSH
• myši MeSH
• peritoneální makrofágy cytologie   účinky léků   MeSH
• průtoková cytometrie MeSH
• rekombinantní proteiny MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• faktor stimulující granulocyto-makrofágové kolonie MeSH
• faktor stimulující kolonie makrofágů MeSH
• fibronektiny MeSH
• Freundovo adjuvans MeSH
• rekombinantní proteiny MeSH

If misregulated, macrophage (Mϕ)-T cell interactions can drive chronic inflammation thereby causing diseases, such as rheumatoid arthritis (RA). We report that in a proinflammatory environment, granulocyte-Mϕ (GM-CSF)- and Mϕ colony-stimulating factor (M-CSF)-dependent Mϕs have dichotomous effects on T cell activity. While GM-CSF-dependent Mϕs show a highly stimulatory activity typical for M1 Mϕs, M-CSF-dependent Mϕs, marked by folate receptor β (FRβ), adopt an immunosuppressive M2 phenotype. We find the latter to be caused by the purinergic pathway that directs release of extracellular ATP and its conversion to immunosuppressive adenosine by co-expressed CD39 and CD73. Since we observed a misbalance between immunosuppressive and immunostimulatory Mϕs in human and murine arthritic joints, we devised a new strategy for RA treatment based on targeted delivery of a novel methotrexate (MTX) formulation to the immunosuppressive FRβ+CD39+CD73+ Mϕs, which boosts adenosine production and curtails the dominance of proinflammatory Mϕs. In contrast to untargeted MTX, this approach leads to potent alleviation of inflammation in the murine arthritis model. In conclusion, we define the Mϕ extracellular purine metabolism as a novel checkpoint in Mϕ cell fate decision-making and an attractive target to control pathological Mϕs in immune-mediated diseases.

• Klíčová slova
• adenosine, chronic inflammation, macrophage polarization, macrophage-T cell interaction, methotrexate, purine metabolism, rheumatoid arthritis,
• MeSH
• adenosin imunologie   MeSH
• buněčná diferenciace * MeSH
• faktor stimulující granulocyto-makrofágové kolonie farmakologie   MeSH
• faktor stimulující kolonie makrofágů farmakologie   MeSH
• imunosupresiva aplikace a dávkování   terapeutické užití   MeSH
• lidé MeSH
• makrofágy imunologie   metabolismus   MeSH
• methotrexát aplikace a dávkování   terapeutické užití   MeSH
• modely nemocí na zvířatech MeSH
• monocyty účinky léků   MeSH
• myši MeSH
• proliferace buněk MeSH
• puriny metabolismus   MeSH
• revmatoidní artritida farmakoterapie   imunologie   MeSH
• synoviální tekutina cytologie   imunologie   MeSH
• zánět farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosin MeSH
• faktor stimulující granulocyto-makrofágové kolonie MeSH
• faktor stimulující kolonie makrofágů MeSH
• imunosupresiva MeSH
• methotrexát MeSH
• puriny MeSH

Amyloid formation depends on amyloid precursor production and is influenced by the activity of the underlying disorder and mediated by some proinflammatory cytokines. In this pilot study we tried to find some specific markers that could establish the activity of the disease. We investigated 45 samples of sera and 38 samples of urine from patients (pts) with secondary amyloidosis (AA), primary amyloidosis (AL), systemic autoimmune diseases with renal impairment (Vasc) and healthy controls (Co). Pts with AA had increased plasma levels of TNF alpha (9.97 +/- 4.22 vs. 2.63 +/- 1.34 pg/mL, p < 0.001) and SAA (43.14 +/- 16.0 vs. 3.42 +/- 0.7 ng/mL, p < 0.05) in comparison with Co. Plasma levels of M-CSF in the AA group were significantly increased in comparison with Co (1077.34 +/- 238.6 vs. 137.71 +/- 19.6, pg/mL, p < 0.001) and also in comparison with Vasc (482.24 +/- 86.7 pg/mL, p < 0.05). Urinary excretions of TNF alpha (8.92 +/- 8.1 vs. 0.17 +/- 0.11 microgram/mol creatinine, p < 0.01), sIL-6R (1.39 +/- 1.14 vs. 0.07 +/- 0.05 g/mol creatinine, p < 0.01) and M-CSF (650.2 +/- 153.7 vs. 33.3 +/- 8.6 micrograms/mol creatinine, p < 0.01) in AA were significantly increased in comparison with Co. Pts with AL had increased plasma levels of M-CSF (819.83 +/- 264.2 vs. 137.71 +/- 19.6 pg/mL, p < 0.05) and urinary excretion of M-CSF (865.0 +/- 188.4 vs. 33.3 +/- 8.6 micrograms/mol creatinine, p < 0.01) in comparison with Co. SAA has a low specificity for amyloidosis but is a sensitive acute phase reactant. TNF alpha, a proinflammatory cytokine, may reflect the activity of the underlying diseases in secondary amyloidosis. M-CSF was increased both in plasma and urine in amyloidosis groups and seems to be the most promising (possibly specific) marker of amyloidosis.

• MeSH
• amyloid metabolismus   MeSH
• amyloidóza krev   moč   MeSH
• analýza rozptylu MeSH
• autoimunitní nemoci krev   moč   MeSH
• biologické markery MeSH
• cytokiny krev   moč   MeSH
• ELISA MeSH
• faktor stimulující kolonie makrofágů krev   MeSH
• lidé MeSH
• sérový amyloid A metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• amyloid MeSH
• biologické markery MeSH
• cytokiny MeSH
• faktor stimulující kolonie makrofágů MeSH
• sérový amyloid A MeSH

BACKGROUND: Dialysis related amyloidosis (DRA) is a severe complication of the long-term dialysis treatment. beta 2 microglobulin and probably other factors influence the development of amyloid deposits. We investigated some of these factors during hemodialysis session. METHODS AND RESULTS: We investigated 20 patients undergoing regular hemodialysis treatment. Patients were divided into AMYL group (with histologically proven DRA) and NE-AMYL group (without signs of DRA). Plasma levels of following factors were investigated using standard ELISA kits: serum amyloid A (SAA), interleukin-6 (IL-6), macrophage-colony stimulating factor (M-CSF). In addition plasma concentrations of C-reactive protein (CRP) and beta 2 microglobulin (beta 2M) were investigated in the AMYL group. All these parameters were studied during different time periods of the hemodialysis session. Plasma levels of SAA and IL-6 did not increase during hemodialysis session and we did not find any difference in plasma levels of these factors between the group of patients with AMYLand NE-AMYL. Plasma levels of M-CSF increased during hemodialysis and its levels in AMYL group were significantly higher in comparison with NE-AMYL group at the end of hemodialysis session (5345.10 +/- 340.42 vs. 3458.45 +/- 332.15 pg/ml, p = 0.0011). A linear correlation was found between plasma levels of SAA and CRP during hemodialysis whereas no correlation was found between plasma levels of beta 2M and other factors. CONCLUSIONS: Our study suggests that plasma levels of M-CSF are increased in patients with chronic renal failure. Significant increase of M-CSF levels in the AMYL group could lead to greater activation of monocyte-macrophage system and could serve as factor supporting amyloid deposition process.

• MeSH
• amyloidóza krev   etiologie   MeSH
• beta-2-mikroglobulin krev   MeSH
• C-reaktivní protein analýza   MeSH
• cytokiny krev   MeSH
• dialýza ledvin škodlivé účinky   MeSH
• faktor stimulující kolonie makrofágů krev   MeSH
• interleukin-6 krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• sérový amyloid A analýza   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• beta-2-mikroglobulin MeSH
• C-reaktivní protein MeSH
• cytokiny MeSH
• faktor stimulující kolonie makrofágů MeSH
• interleukin-6 MeSH
• sérový amyloid A MeSH

Bordetella pertussis infects human upper airways and deploys an array of immunosuppressive virulence factors, among which the adenylate cyclase toxin (CyaA) plays a prominent role in disarming host phagocytes. CyaA binds the complement receptor-3 (CR3 aka αMβ2 integrin CD11b/CD18 or Mac-1) of myeloid cells and delivers into their cytosol an adenylyl cyclase enzyme that hijacks cellular signaling through unregulated conversion of cytosolic ATP to cAMP. We found that the action of as little CyaA as 22 pM (4 ng/mL) blocks macrophage colony-stimulating factor (M-CSF)-driven transition of migratory human CD14+ monocytes into macrophages. Global transcriptional profiling (RNAseq) revealed that exposure of monocytes to 22 pM CyaA for 40 hours in culture with 20 ng/mL of M-CSF led to upregulation of genes that exert negative control of monocyte to macrophage differentiation (e.g., SERPINB2, DLL1, and CSNK1E). The sustained CyaA action yielded downregulation of numerous genes involved in processes crucial for host defense, such as myeloid cell differentiation, chemotaxis of inflammatory cells, antigen presentation, phagocytosis, and bactericidal activities. CyaA-elicited signaling also promoted deacetylation and trimethylation of lysines 9 and 27 of histone 3 (H3K9me3 and H3K27me3) and triggered the formation of transcriptionally repressive heterochromatin patches in the nuclei of CyaA-exposed monocytes. These effects were partly reversed by the G9a methyltransferase inhibitor UNC 0631 and by the pleiotropic HDAC inhibitor Trichostatin-A, revealing that CyaA-elicited epigenetic alterations mediate transcriptional reprogramming of monocytes and play a role in CyaA-triggered block of monocyte differentiation into bactericidal macrophage cells.IMPORTANCETo proliferate on host airway mucosa and evade elimination by patrolling sentinel cells, the whooping cough agent Bordetella pertussis produces a potently immunosubversive adenylate cyclase toxin (CyaA) that blocks opsonophagocytic killing of bacteria by phagocytes like neutrophils and macrophages. Indeed, chemotactic migration of CD14+ monocytes to the infection site and their transition into bactericidal macrophages, thus replenishing the exhausted mucosa-patrolling macrophages, represents one of the key mechanisms of innate immune defense to infection. We show that the cAMP signaling action of CyaA already at a very low toxin concentration triggers massive transcriptional reprogramming of monocytes that is accompanied by chromatin remodeling and epigenetic histone modifications, which block the transition of migratory monocytes into bactericidal macrophage cells. This reveals a novel layer of toxin action-mediated hijacking of functional differentiation of innate immune cells for the sake of mucosal pathogen proliferation and transmission to new hosts.

• Klíčová slova
• Bordetella pertussis, RTX toxins, cyclic AMP, differentiation, epigenetics, macrophages, monocytes,
• MeSH
• adenylátcyklasový toxin * metabolismus   MeSH
• Bordetella pertussis * patogenita   enzymologie   MeSH
• buněčná diferenciace * účinky léků   MeSH
• faktor stimulující kolonie makrofágů MeSH
• kultivované buňky MeSH
• lidé MeSH
• makrofágy * účinky léků   cytologie   MeSH
• monocyty * účinky léků   cytologie   fyziologie   MeSH
• přeprogramování buněk * MeSH
• restrukturace chromatinu * účinky léků   MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenylátcyklasový toxin * MeSH
• faktor stimulující kolonie makrofágů MeSH

Co-cultures of osteoblasts and osteoclasts are on the rise because they enable a more complex study. Diseases such as osteoporosis are related to a higher age. Thus, cell isolation from adult individuals is necessary. Osteoblasts can be isolated from the rat femur by three methods: explant culture, explant culture with enzymatic pre-treatment, or enzymatic treatment. The isolation methods yield different populations of osteoblasts which, in a co-culture with peripheral blood mononuclear cells, might result in differences in osteoclastogenesis. Therefore, we examined the differences in osteogenic markers, cell proliferation, and the metabolic activity of isolated osteoblast-like cells in a growth and differentiation medium. We then evaluated the effect of the isolated populations of osteoblast-like cells on osteoclastogenesis in a subsequent co-culture by evaluating osteoclast markers, counting formed osteoclast-like cells, and analyzing their area and number of nuclei. Co-cultures were performed in the presence or absence of osteoclastogenic growth factors, M-CSF and RANKL. It was discovered that enzymatic isolation is not feasible in adult rats, but explant culture and explant culture with enzymatic pre-treatment were both successful. Explant culture with enzymatic pre-treatment yielded cells with a higher proliferation than explant culture in a growth medium. The differentiation medium reduced differences in proliferation during the culture. Some differences in metabolic activity and ALP activity were also found between the osteoblast-like cells isolated by explant culture or by explant culture with enzymatic pre-treatment, but only on some days of cultivation. According to microscopy, the presence of exogenous growth factors supporting osteoclastogenesis in co-cultures was necessary for the formation of osteoclast-like cells. In this case, the formation of a higher number of osteoclast-like cells with a larger area was observed in the co-culture with osteoblast-like cells isolated by explant culture compared to the explant culture with enzymatic pre-treatment. Apart from this observation, no differences in osteoclast markers were noted between the co-cultures with osteoblast-like cells isolated by explant culture and the explant culture with enzymatic pre-treatment. The TRAP and CA II activity was higher in the co-cultures with exogenous growth than that in the co-cultures without exogenous growth factors on day 7, but the opposite was true on day 14. To conclude, explant culture and explant culture with enzymatic pre-treatment are both suitable methods to yield osteoblast-like cells from adult rats capable of promoting osteoclastogenesis in a direct co-culture with peripheral blood mononuclear cells. Explant culture with enzymatic pre-treatment yielded cells with a higher proliferation. The explant culture yielded osteoblast-like cells which induced the formation of a higher number of osteoclast-like cells with a larger area compared to the explant culture with enzymatic pre-treatment when cultured with exogenous M-CSF and RANKL.

• Klíčová slova
• adult rat, co-culture, mature bone, osteoblast-like cell, osteoclast-like cell,
• MeSH
• buněčná diferenciace MeSH
• faktor stimulující kolonie makrofágů * metabolismus   MeSH
• kokultivační techniky MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• leukocyty mononukleární metabolismus   MeSH
• ligand RANK metabolismus   MeSH
• osteoblasty metabolismus   MeSH
• osteogeneze * MeSH
• osteoklasty metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• faktor stimulující kolonie makrofágů * MeSH
• ligand RANK MeSH

Monoclonal antibody 2A4 against human heart ferritin and a polyclonal antibody against human placental ferritin inactivated the suppressor activity present in media conditioned by cells of patients with myelodysplastic syndrome (MDS). These antibodies also neutralized the inhibitory activity released by cells of myeloid leukemic ML-2 cell line. In contrast, a monoclonal antibody against the ferritin L subunit did not neutralize the inhibitory activity of the media conditioned either by the cells of patients with MDS or by the ML-2 cell line. Neutralization of the inhibitory activity present in supernatants of cells of MDS patients and the ML-2 cell line by monoclonal antibodies against the H subunit of ferritin strongly indicates that the inhibitory activity resides in the acidic isoferritin molecule.

• MeSH
• antisérum imunologie   MeSH
• faktor stimulující granulocyto-makrofágové kolonie farmakologie   MeSH
• faktor stimulující kolonie makrofágů farmakologie   MeSH
• ferritiny imunologie   MeSH
• kultivační média MeSH
• lidé MeSH
• monoklonální protilátky imunologie   MeSH
• myelodysplastické syndromy metabolismus   patologie   MeSH
• myeloidní leukemie metabolismus   patologie   MeSH
• nádorové buňky kultivované MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antisérum MeSH
• faktor stimulující granulocyto-makrofágové kolonie MeSH
• faktor stimulující kolonie makrofágů MeSH
• ferritiny MeSH
• kultivační média MeSH
• monoklonální protilátky MeSH