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Activating and inhibitory immune receptors play a critical role in regulating systemic and central nervous system (CNS) immune and inflammatory processes. The CD200R1 immunoreceptor induces a restraining signal modulating inflammation and phagocytosis in the CNS under different inflammatory conditions. However, it remains unknown whether CD200R1 has a role in modulating the inflammatory response after a peripheral nerve injury, an essential component of the successful regeneration. Expression of CD200R1 and its ligand CD200 was analyzed during homeostasis and after a sciatic nerve crush injury in C57Bl/6 mice. The role of CD200R1 in Wallerian Degeneration (WD) and nerve regeneration was studied using a specific antibody against CD200R1 injected into the nerve at the time of injury. We found an upregulation of CD200R1 mRNA after injury whereas CD200 was downregulated acutely after nerve injury. Blockade of CD200R1 significantly reduced the acute entrance of both neutrophils and monocytes from blood after nerve injury. When long term regeneration and functional recovery were evaluated, we found that blockade of CD200R1 had a significant effect impairing the spontaneous functional recovery. Taken together, these results show that CD200R1 has a role in mounting a successful acute inflammatory reaction after injury, and contributes to an effective functional recovery.

Assuntos

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CD200 (OX-2) is expressed in myeloid cells, B cells, subsets of T cells and on other normal and neoplastic non-hematopoietic cells. It interacts with CD200R and has a suppressive effect on T cells immune mediated response. We aimed to review CD200 expression and its role in the immune evasion of non-B cell hematopoietic neoplasms. In acute myeloid leukemia, CD200 seems to be related to the worst outcome, even in diseases of good prognosis, possibly due to an immunosuppressive effect. In plasma cell myeloma studies, while some have associated CD200 expression with worst prognosis possibly due to its suppressive effect on monocyte and T cell-mediated immune response, in others CD200 appeared to be a marker of a better outcome, or even showed no impact in event-free survival (EFS). Few studies have evaluated CD200 expression in T cell neoplasms; however, it appears to be a good immunophenotypic marker for angioimmunoblastic T cell lymphoma. In conclusion, CD200 appears to be involved in the immune evasion of malignant cells, which could affect the survival of these patients.

Assuntos

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Flow cytometric cell surface proteomics provides a new and powerful tool to determine changes accompanying neoplastic transformation and invasion, providing clues to essential interactions with the microenvironment as well as leads for potential therapeutic targets. One of the most important advantages of flow cytometric cell surface proteomics is that it can be performed on living cells that can be sorted for further characterization and functional studies. Here, we document the surface proteome of clonogenic metastatic breast cancer (MBrCa) explants, which was strikingly similar to that of normal mesenchymal stromal cells (P = 0.017, associated with Pearson correlation coefficient) and transformed mammary epithelial cells (P = 0.022). Markers specifically upregulated on MBrCa included CD200 (Ox2), CD51/CD61 (Integrin α5/ß3), CD26 (dipeptidyl peptidase-4), CD165 (c-Cbl), and CD54 (ICAM-1). Proteins progressively upregulated in a model of neoplastic transformation and invasion included CD26, CD63 (LAMP3), CD105 (Endoglin), CD107a (LAMP1), CD108 (Semaphorin 7A), CD109 (Integrin ß4), CD151 (Raph blood group), and disialoganglioside G2. The proteome of the commonly used cell lines MDA-MB-231, MCF7, and BT-474 were uncorrelated with that of MBrCa (P = 1.0, 1.0, 0.9, respectively). The comparison has demonstrated the mesenchymal nature of clonogenic cells isolated by short-term culture of metastatic breast cancer, provided several leads for biomarkers and potential targets for anti-invasive therapy, including CD200, and highlighted the limitations of breast cancer cell lines for representing the cell surface biology of breast cancer. © 2017 International Society for Advancement of Cytometry.

Assuntos

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Abstract Background Distinction between mature B-cell neoplasms can be difficult due to overlapping of immunologic features and clinical manifestations. This study investigated whether quantifying mean fluorescence intensity of four monoclonal antibodies in a flow cytometry panel is useful for the differential diagnosis and characterization of these disorders. Methods The expressions of CD52, CD200, CD123 and CD43 were analyzed in samples from 124 patients with mature B-cell neoplasms. The quantitative estimation of these antigens was assessed by mean fluorescence intensity. Results The cases included were 78 chronic lymphocytic leukemias, three atypical chronic lymphocytic leukemias, six marginal zone lymphomas, 11 splenic marginal zone lymphomas, nine lymphoplasmacytic lymphomas, six mantle cell lymphomas, two hairy cell leukemias, two hairy cell leukemias variant, five follicular lymphomas, one Burkitt lymphoma and one diffuse large B-cell lymphoma. The mean fluorescence intensity of CD200 was higher in atypical chronic lymphocytic leukemia, chronic lymphocytic leukemia and hairy cell leukemia cases. CD123 showed higher mean fluorescence intensities in hairy cell leukemia cells. Chronic lymphocytic leukemia, atypical chronic lymphocytic leukemia and mantle cell lymphoma had higher expression of CD43 and all follicular lymphoma cases had very low mean fluorescence intensity values. CD52 expression was consistently positive among all cases. Conclusion Quantitative evaluation of these markers can be a useful additional tool to better identify some types of mature B-cell neoplasms.

Assuntos

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BACKGROUND: Distinction between mature B-cell neoplasms can be difficult due to overlapping of immunologic features and clinical manifestations. This study investigated whether quantifying mean fluorescence intensity of four monoclonal antibodies in a flow cytometry panel is useful for the differential diagnosis and characterization of these disorders. METHODS: The expressions of CD52, CD200, CD123 and CD43 were analyzed in samples from 124 patients with mature B-cell neoplasms. The quantitative estimation of these antigens was assessed by mean fluorescence intensity. RESULTS: The cases included were 78 chronic lymphocytic leukemias, three atypical chronic lymphocytic leukemias, six marginal zone lymphomas, 11 splenic marginal zone lymphomas, nine lymphoplasmacytic lymphomas, six mantle cell lymphomas, two hairy cell leukemias, two hairy cell leukemias variant, five follicular lymphomas, one Burkitt lymphoma and one diffuse large B-cell lymphoma. The mean fluorescence intensity of CD200 was higher in atypical chronic lymphocytic leukemia, chronic lymphocytic leukemia and hairy cell leukemia cases. CD123 showed higher mean fluorescence intensities in hairy cell leukemia cells. Chronic lymphocytic leukemia, atypical chronic lymphocytic leukemia and mantle cell lymphoma had higher expression of CD43 and all follicular lymphoma cases had very low mean fluorescence intensity values. CD52 expression was consistently positive among all cases. CONCLUSION: Quantitative evaluation of these markers can be a useful additional tool to better identify some types of mature B-cell neoplasms.

RESUMO

BACKGROUND: Pro-inflammatory and oxidative events during brain Venezuelan equine encephalitis virus infection could lead to apoptosis and induce anti-inflammatory responses (increased expression of CD200). The aim of this study was to determine the effect of melatonin on brain apoptosis, oxidative stress, and CD200 molecule in mice and neuroblastoma cultures infected by Venezuelan equine encephalitis virus. METHODS: Mice were infected with 10 median lethal doses (LD50) of Venezuelan equine encephalitis virus, treated with melatonin (500 µg/kg bw; three days before infection and during all experimental time) and sacrificed on days 1, 3, and 5 postinfection. Brain samples were obtained at those periods of time. In addition, infected neuroblastoma cell cultures (multiplicity of infection [MOI]: 1) were treated with 0, 0.1, 0.5, and 1 mM of melatonin and analyzed at 2, 4, and 6 h. CD200 and apoptosis expressions were analyzed by immunohistochemistry and TUNEL assay, respectively. Nitrites and malondialdehyde were determined by appropriate biochemical methods. RESULTS: Increased brain expression of apoptosis, nitrite, and malondialdehyde productions and CD200 of infected mice were found. Melatonin diminished those expressions. Similarly, high apoptosis expression and nitrite and malondialdehyde productions on infected neuroblastoma cultures were diminished by melatonin. Melatonin increased the survival rate (25%) in Venezuelan equine encephalitis virus-infected animals compared with untreated infected mice (0%). CONCLUSIONS: Neurological damage during brain Venezuelan equine encephalitis virus infection could be mediated by apoptosis and oxidative stress and CD200 molecule could be an important anti-inflammatory response. Melatonin could be beneficial reducing apoptosis and oxidative stress.

Assuntos

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BACKGROUND: Multiparameter flow cytometry is a useful tool for the diagnostic evaluation of mature B-cell neoplasms (MBN). Recently, it has been shown that CD200 may improve the distinction between chronic lymphocytic leukemia (CLL; CD200+) and mantle cell lymphoma (MCL; CD200-), but the role of CD200 expression in atypical CLL and other MBN remains to be established. METHODS: To address this issue, we investigated the expression of CD200 in 159 consecutive cases of MBN. RESULTS: CD200 was strongly expressed in CLL and was revealed to be an excellent marker to distinguish CLL from MCL, even in cases of atypical CLL. However, lack of CD200 was not an exclusive finding of MCL, being also observed in other MBNs. Furthermore, CD200 was highly expressed in hairy cell leukemia, being useful in the differential diagnosis of lymphomas with villous lymphocytes. Herein, we propose an algorithm to classify CD5+ MBNs based on the expression of CD200, CD11c, heavy chain immunoglobulins, and Matutes score. CONCLUSIONS: These results expand the understanding of the CD200 expression in MBNs, giving further support for the inclusion of this marker in the routine investigation by flow cytometry.

Assuntos

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Background: Multiparameter flow cytometry is a useful tool for the diagnostic evaluation of mature B-cell neoplasms (MBN). Recently, it has been shown that CD200 may improve the distinction between chronic lymphocytic leukemia (CLL; CD200+) and mantle cell lymphoma (MCL; CD200-), but the role of CD200 expression in atypical CLL and other MBN remains to be established. Methods: To address this issue, we investigated the expression of CD200 in 159 consecutive cases of MBN. Results: CD200 was strongly expressed in CLL and was revealed to be an excellent marker to distinguish CLL from MCL, even in cases of atypical CLL. However, lack of CD200 was not an exclusive finding of MCL, being also observed in other MBNs. Furthermore, CD200 was highly expressed in hairy cell leukemia, being useful in the differential diagnosis of lymphomas with villous lymphocytes. Herein, we propose an algorithm to classify CD5+ MBNs based on the expression of CD200, CD11c, heavy chain immunoglobulins and Matutes score. Conclusions: These results expand the understanding of the CD200 expression in MBNs, giving further support for the inclusion of this marker in the routine investigation by flow cytometry. © 2013 Clinical Cytometry Society.