OBJECTIVE: We measured and compared changes in the percentage of cells expressing CD80, CD86, CD40, HLA-DR and the expression of these molecules on B cells and monocytes of patients who underwent either on-pump, mini on-pump or off-pump cardiac surgery. METHODS: Blood samples from patients who underwent either on-pump, mini on-pump or off-pump cardiac surgery were collected before surgery, instantly after surgery and on the 1(st), 3(rd) and 7(th) days after surgery. Surface expression of CD80, CD86, CD40 and HLA-DR molecules was determined by flow cytometry. RESULTS: Our results show that all three surgical techniques altered the expression of these molecules, as well as the percentage relative number of specific cell populations. We identified statistically significant differences when comparing different surgical techniques. On-pump surgery revealed a more pronounced impact on the phenotype of immune system cells than the other techniques. Therefore, it is likely that the function of immune cells is changed the most by on-pump surgery. We found a lower decrease in the number of CD80(+) monocytes and a lower drop in the CD40 expression on monocytes in off-pump patients in comparison with on-pump patients. CONCLUSION: All the types of cardiac surgical techniques, off-pump, on-pump and modified mini-invasive on-pump, are associated with changes in CD80, CD86, CD40 and HLA-DR expression. We found several significant differences in the expression of the selected molecules when we compared all three groups of patients.

• MeSH
• antigeny CD40 analýza   MeSH
• antigeny CD80 analýza   MeSH
• antigeny CD86 analýza   MeSH
• B-lymfocyty imunologie   MeSH
• HLA-DR antigeny analýza   MeSH
• kardiochirurgické výkony * MeSH
• lidé středního věku MeSH
• lidé MeSH
• monocyty imunologie   MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Optimal discrimination between leukemic blasts and normal B-cell precursors (BCP) is critical for treatment monitoring in BCP acute lymphoblastic leukemia (ALL); thus identification of markers differentially expressed on normal BCP and leukemic blasts is required. METHODS: Multicenter analysis of CD73, CD86 and CD304 expression levels was performed in 282 pediatric BCP-ALL patients vs. normal bone marrow BCP, using normalized median fluorescence intensity (nMFI) values. RESULTS: CD73 was expressed at abnormally higher levels (vs. pooled normal BCP) at diagnosis in 71/108 BCP-ALL patients (66%), whereas CD304 and CD86 in 119/202 (59%) and 58/100 (58%) patients, respectively. Expression of CD304 was detected at similar percentages in common-ALL and pre-B-ALL, while found at significantly lower frequencies in pro-B-ALL. A significant association (p = 0.009) was found between CD304 expression and the presence of the ETV6-RUNX1 fusion gene. In contrast, CD304 showed an inverse association with MLL gene rearrangements (p = 0.01). The expression levels of CD73, CD86 and CD304 at day 15 after starting therapy (MRD15) were stable or higher than at diagnosis in 35/37 (95%), 40/56 (71%) and 19/41 (46%) cases investigated, respectively. This was also associated with an increased mean nMFI at MRD15 vs. diagnosis of +24 and +3 nMFI units for CD73 and CD86, respectively. In addition, gain of expression of CD73 and CD86 at MRD15 for cases that were originally negative for these markers at diagnosis was observed in 16% and 18% of cases, respectively. Of note, CD304 remained aberrantly positive in 63% of patients, despite its levels of expression decreased at follow-up in 54% of cases. CONCLUSIONS: Here we show that CD73, CD86 and CD304 are aberrantly (over)expressed in a substantial percentage of BCP-ALL patients and that their expression profile remains relatively stable early after starting therapy, supporting their potential contribution to improved MRD analysis by flow cytometry.

• MeSH
• 5'-nukleotidasa analýza   biosyntéza   MeSH
• antigeny CD86 analýza   biosyntéza   MeSH
• dítě MeSH
• GPI-vázané proteiny analýza   biosyntéza   MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• neuropilin-1 analýza   biosyntéza   MeSH
• pre-B-buněčná leukemie patologie   MeSH
• předškolní dítě MeSH
• prekurzorové B-lymfoidní buňky patologie   MeSH
• reziduální nádor MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH

• MeSH
• antigeny CD80 MeSH
• antigeny CD86 MeSH
• imunitní systém MeSH
• lidé MeSH
• myši MeSH
• regulační T-lymfocyty * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH

To ensure successful feeding tick saliva contains a number of inhibitory proteins that interfere with the host immune response and help to create a permissive environment for pathogen transmission. Among the potential targets of the salivary cystatins are two host cysteine proteases, cathepsin S, which is essential for antigen- and invariant chain-processing, and cathepsin C (dipeptidyl peptidase 1, DPP1), which plays a critical role in processing and activation of the granule serine proteases. Here, the effect of salivary cystatin OmC2 fromOrnithodoros moubatawas studied using differentiated MUTZ-3 cells as a model of immature dendritic cells of the host skin. Following internalization, cystatin OmC2 was initially found to inhibit the activity of several cysteine cathepsins, as indicated by the decreased rates of degradation of fluorogenic peptide substrates. To identify targets, affinity chromatography was used to isolate His-tagged cystatin OmC2 together with the bound proteins from MUTZ-3 cells. Cathepsins S and C were identified in these complexes by mass spectrometry and confirmed by immunoblotting. Furthermore, reduced increase in the surface expression of MHC II and CD86, which are associated with the maturation of dendritic cells, was observed. In contrast, human inhibitor cystatin C, which is normally expressed and secreted by dendritic cells, did not affect the expression of CD86. It is proposed that internalization of salivary cystatin OmC2 by the host dendritic cells targets cathepsins S and C, thereby affecting their maturation.

• MeSH
• antigeny CD86 MeSH
• antigeny diferenciační B-lymfocytární MeSH
• buněčné linie MeSH
• cystatiny metabolismus   MeSH
• dendritické buňky imunologie   metabolismus   MeSH
• epoxidové sloučeniny imunologie   metabolismus   MeSH
• geny MHC třídy II imunologie   MeSH
• kathepsin C metabolismus   MeSH
• kathepsiny chemie   imunologie   metabolismus   MeSH
• klíšťata enzymologie   MeSH
• lidé MeSH
• lyzozomy enzymologie   MeSH
• MHC antigeny II. třídy MeSH
• Ornithodoros enzymologie   MeSH
• rekombinantní proteiny MeSH
• sliny enzymologie   MeSH
• tyrosin analogy a deriváty   imunologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

To elucidate the role of innate immune responses in celiac disease, we investigated the effect of gliadin on blood monocytes from patients with celiac disease. Gliadin induced substantial TNF-alpha and IL-8 production by monocytes from patients with active celiac disease, lower levels by monocytes from patients with inactive celiac disease, and even lower levels by monocytes from healthy donors. In healthy donor monocytes gliadin induced IL-8 from monocytes expressing HLA-DQ2 and increased monocyte expression of the costimulatory molecules CD80 and CD86, the dendritic cell marker CD83, and the activation marker CD40. Gliadin also increased DNA binding activity of NF-kappaB p50 and p65 subunits in monocytes from celiac patients, and NF-kappaB inhibitors reduced both DNA binding activity and cytokine production. Thus, gliadin activation of HLA-DQ2(+) monocytes leading to chemokine and proinflammatory cytokine production may contribute to the host innate immune response in celiac disease.

• MeSH
• aktivace makrofágů imunologie   MeSH
• antigeny CD40 metabolismus   MeSH
• antigeny CD80 metabolismus   MeSH
• antigeny CD86 metabolismus   MeSH
• CD antigeny metabolismus   MeSH
• celiakie imunologie   metabolismus   MeSH
• cytokiny biosyntéza   MeSH
• financování organizované MeSH
• gliadin metabolismus   MeSH
• HLA-DQ antigeny metabolismus   MeSH
• imunoglobuliny metabolismus   MeSH
• interleukin-8 biosyntéza   MeSH
• lidé MeSH
• membránové glykoproteiny metabolismus   MeSH
• monocyty metabolismus   MeSH
• NF-kappa B metabolismus   MeSH
• peptidové fragmenty MeSH
• průtoková cytometrie MeSH
• TNF-alfa biosyntéza   MeSH
• Check Tag
• lidé MeSH

We investigated the effect of a Multiwave Locked System laser (with a simultaneous 808 nm continuous emission and 905 nm pulse emission) on the spinal cord after spinal cord injury (SCI) in rats. The functional recovery was measured by locomotor tests (BBB, Beam walking, MotoRater) and a sensitivity test (Plantar test). The locomotor tests showed a significant improvement of the locomotor functions of the rats after laser treatment from the first week following lesioning, compared to the controls. The laser treatment significantly diminished thermal hyperalgesia after SCI as measured by the Plantar test. The atrophy of the soleus muscle was reduced in the laser treated rats. The histopathological investigation showed a positive effect of the laser therapy on white and gray matter sparing. Our data suggests an upregulation of M2 macrophages in laser treated animals by the increasing number of double labeled CD68+/CD206+ cells in the cranial and central parts of the lesion, compared to the control animals. A shift in microglial/macrophage polarization was confirmed by gene expression analysis by significant mRNA downregulation of Cd86 (marker of inflammatory M1), and non-significant upregulation of Arg1 (marker of M2). These results demonstrated that the combination of 808 nm and 905 nm wavelength light is a promising non-invasive therapy for improving functional recovery and tissue sparing after SCI.

• MeSH
• antigeny CD86 genetika   metabolismus   MeSH
• antigeny diferenciační myelomonocytární genetika   metabolismus   MeSH
• CD antigeny genetika   metabolismus   MeSH
• krysa rodu rattus MeSH
• laserová terapie s nízkou intenzitou světla metody   MeSH
• lektiny typu C genetika   metabolismus   MeSH
• lektiny vázající mannosu genetika   metabolismus   MeSH
• lokomoce MeSH
• mícha metabolismus   patologie   MeSH
• poranění míchy terapie   MeSH
• potkani Wistar MeSH
• receptory buněčného povrchu genetika   metabolismus   MeSH
• regenerace míchy MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

N-acetyl-D-glucosamine-coated polyamidoamine dendrimer (GN8P), exerting high binding affinity to rodent recombinant NKR-P1A and NKR-P1C activating proteins, was shown previously to delay the development of rat colorectal carcinoma as well as mouse B16F10 melanoma, and to potentiate antigen-specific antibody formation in healthy C57BL/6 mice via NK cell stimulation. In this study, we investigated whether GN8P also modulates tumor-specific B cell responses. Serum anti-B16F10 melanoma IgG levels, IgG2a mRNA expression, antibody dependent cell-mediated cytotoxicity (ADCC), and counts of plasma as well as antigen presenting B cells were evaluated in tumor-bearing C57BL/6 mice treated with GN8P and in respective controls. To reveal the mechanism of GN8P effects, the synthesis of interferon-gamma (IFN-γ) and interleukin-4 (IL-4), cytokines involved in regulation of immunoglobulin class switch, was determined. The GN8P treatment significantly elevated IgG, and particularly IgG2a, response against B16F10 melanoma, which led to augmented ADCC reaction. The significant increase in production of IFN-γ, which is known to support IgG2a secretion, was observed solely in NK1.1 expressing cell populations, predominantly in NK cells. Moreover, GN8P raised the number of plasma cells, and promoted antigen presenting capacity of I-A/I-E-positive B lymphocytes by up-regulation of their CD80 and CD86 co-stimulatory molecule expression. These results indicate that GN8P-induced enhancement of tumor-specific antibody formation is triggered by NK cell activation, and contributes to complexity of anticancer immune response involving lectin-saccharide interaction.

• MeSH
• acetylglukosamin chemie   farmakologie   MeSH
• antigeny CD80 biosyntéza   genetika   MeSH
• antigeny CD86 biosyntéza   genetika   MeSH
• B-lymfocyty účinky léků   imunologie   metabolismus   MeSH
• buněčná cytotoxicita závislá na protilátkách účinky léků   imunologie   MeSH
• buňky NK účinky léků   imunologie   metabolismus   MeSH
• dendrimery chemie   farmakologie   MeSH
• imunoglobulin G biosyntéza   krev   genetika   imunologie   MeSH
• interferon gama biosyntéza   genetika   MeSH
• interleukin-4 biosyntéza   genetika   MeSH
• melanom experimentální genetika   imunologie   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• up regulace účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Treatment of murine EL4 T cell lymphoma with N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates of doxorubicin (Dox) leads to complete tumor regression and to the development of therapy-dependent longlasting cancer resistance. This phenomenon occurs with two types of Dox conjugates tested, despite differences in the covalent linkage of Dox to the polymer carrier. Such a cancer resistance cannot fully express in conventional treatment with free Dox, due to substantial immunotoxicity of the treatment, which was not observed in the polymer conjugates. In this study, calreticulin (CRT) translocation and high mobility group box-1 protein (HMGB1) release was observed in EL4 cells treated with a conjugate releasing Dox by a pH-dependent manner. As a result, the treated tumor cells were engulfed by dendritic cells (DC) in vitro, and induced their expression of CD80, CD86, and MHC II maturation markers. Conjugates with Dox bound via an amide bond only increased translocation of HSPs to the membrane, which led to an elevated phagocytosis but was not sufficient to induce increase of the maturation markers on DCs in vitro. Both types of conjugates induced engulfment of the target tumor cells in vivo, that was more intense than that seen with free Dox. It means that the induction of anti-tumor immunity documented upon treatment of EL4 lymphoma with HPMA-bound Dox conjugates does not rely solely on CRT-mediated cell death, but involves multiple mechanisms.

• MeSH
• antigeny CD80 metabolismus   MeSH
• antigeny CD86 metabolismus   MeSH
• apoptóza účinky léků   MeSH
• chemorezistence účinky léků   MeSH
• dendritické buňky cytologie   imunologie   MeSH
• doxorubicin aplikace a dávkování   analogy a deriváty   chemie   toxicita   MeSH
• fagocytóza MeSH
• kalretikulin metabolismus   MeSH
• koncentrace vodíkových iontů MeSH
• kyseliny polymethakrylové aplikace a dávkování   chemie   toxicita   MeSH
• lymfom T-buněčný farmakoterapie   imunologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nosiče léků chemie   MeSH
• protein HMGB1 metabolismus   MeSH
• proteiny teplotního šoku metabolismus   MeSH
• protinádorové látky aplikace a dávkování   chemie   toxicita   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Myeloid-derived suppressor cells (MDSC) play an important role in tumor escape from antitumor immunity. MDSC accumulate in the lymphoid organs and blood during tumor growth and their mobilization was also reported after cyclophosphamide (CY) administration. In this communication, spleen MDSC accumulating after CY therapy (CY-MDSC) were compared with those expanded in mice bearing human papilloma viruses 16-associated TC-1 carcinoma (TU-MDSC). Although both CY-MDSC and TU-MDSC accelerated growth of TC-1 tumors in vivo, their phenotype and immunosuppressive function differed. CY-MDSC consisted of higher percentage of monocyte-like subpopulation and this was accompanied by lower relative expression of immunosuppressive genes and lower suppression of T-cell proliferation. After interferon-γ stimulation, the expression of immunosuppressive genes increased, but the suppressive ability of CY-MDSC did not reach that of TU-MDSC. The phenotype and function of MDSC obtained from mice bearing TC-1 tumors treated with CY was, in general, found to lie between CY-MDSC and TU-MDSC. After in vitro cultivation of MDSC in the presence of interleukin 12 (IL-12), the percentage of CD11b+/Gr-1+ cells decreased and was accompanied by an increase in the percentage of CD86+/MHCII+ cells. The strongest modulatory effect was noticed in the group of CY-MDSC. The susceptibility of CY-MDSC to all-trans-retinoic acid (ATRA) was also evaluated. In vitro cultivation with ATRA resulted in MDSC differentiation, and ATRA inhibited MDSC accumulation induced by CY administration. Our findings identified differences between CY-MDSC and TU-MDSC and supported the rationale for utilization of ATRA or IL-12 to alter MDSC accumulation after CY chemotherapy with the aim to improve its antitumor effect.

• MeSH
• aktivace lymfocytů MeSH
• antigeny CD11b biosyntéza   imunologie   MeSH
• antigeny CD86 biosyntéza   imunologie   MeSH
• buněčná diferenciace účinky léků   MeSH
• cyklofosfamid farmakologie   MeSH
• experimentální nádory imunologie   patologie   virologie   MeSH
• interferon gama farmakologie   MeSH
• interleukin-12 farmakologie   MeSH
• lidé MeSH
• lidský papilomavirus 16 imunologie   MeSH
• myeloidní buňky účinky léků   imunologie   patologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky farmakologie   MeSH
• regulace genové exprese u nádorů MeSH
• slezina účinky léků   imunologie   patologie   MeSH
• T-lymfocyty účinky léků   imunologie   patologie   MeSH
• transplantace nádorů MeSH
• tretinoin farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH