The Experts below are selected from a list of 54 Experts worldwide ranked by ideXlab platform
Robert V. Rouse - One of the best experts on this subject based on the ideXlab platform.
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L-selectin and alpha 4 beta 7 integrin homing receptor pathways mediate peripheral lymphocyte traffic to AKR Mouse hyperplastic thymus.
The American journal of pathology, 1995Co-Authors: Sara A. Michie, Eugene C Butcher, Philip R. Streeter, Robert V. RouseAbstract:Before the development of thymic lymphoma, AKR mice undergo a striking lymphoid hyperplasia of the thymic medulla. We have previously shown that there is a marked increase in traffic of B and T lymphocytes from the periphery into the preneoplastic, hyperplastic thymuses of these mice, in contrast to the scant traffic of such cells to normal thymuses. The traffic of lymphocytes to lymph nodes and Peyer's patches is controlled in part by the interaction of lymphocyte adhesion molecules called homing receptors with their tissue-selective endothelial ligands known as vascular addressins. We have investigated the roles of homing receptors and vascular addressins in the traffic of lymphocytes to the AKR hyperplastic thymus. We demonstrate that development of hyperplasia is accompanied by an increase in the number of thymic medullary blood vessels with high endothelial venule morphology and expression of the peripheral node addressin (PNAd) and the mucosal addressin (MAdCAM-1). In vitro and in vivo functional assays show that the addressin/homing receptor pairs PNAd/L-selectin and MAdCAM-1/alpha 4 beta 7 are involved in lymphocyte traffic to the hyperplastic thymus. These results indicate that molecular adhesion mechanisms involved in tissue-selective migration of lymphocytes to peripheral lymph node and to mucosal lymphoid tissues play a role in the recruitment of B and T lymphocytes to the AKR thymus and thus in the pathogenesis of thymic hyperplasia.
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Macrophages are the first thymic cells to express polytropic retrovirus in AKR Mouse leukemogenesis.
Journal of virology, 1991Co-Authors: S Y Kim, Leonard H. Evans, Frank Malik, Robert V. RouseAbstract:AKR mice spontaneously develop T-cell leukemias in the thymus late in the first year of life. These neoplasms arise following the appearance in the thymus of a recombinant retrovirus but can be prevented by thymectomy, indicating a role for both virus and elements of the thymic microenvironment in leukemogenesis. The intrathymic appearance of recombinant retrovirus was examined at ages leading up to leukemogenesis in order to identify and characterize the microenvironments in which the virus is first expressed. A stromal cell, the macrophage, was found to be the first thymic element to produce detectable levels of recombinant retrovirus, approximately 12 weeks before thymocytes. This observation provides a mechanism to reconcile viral leukemogenesis with the requirement for an intact thymus. Thus, a nonlymphoid cell, the macrophage, may play a critical role in the development of lymphoid neoplasia.
David A. Scheinberg - One of the best experts on this subject based on the ideXlab platform.
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antitumor activity of actinonin in vitro and in vivo
Clinical Cancer Research, 1998Co-Authors: Yang Xu, Janice Gabrilove, David A. ScheinbergAbstract:Actinonin, an antibiotic and CD13/aminopeptidase N (APN) inhibitor, has been shown to be cytotoxic to tumor cell lines in vitro. We investigated the antiproliferative effects of actinonin on human and murine leukemia and lymphoma cells. Actinonin inhibited growth of NB4 and HL60 human cell lines and AKR Mouse leukemia cells in vitro with an IC50 of about 2-5 micrograms/ml. The inhibitory effect on CD13-positive cells was not blocked by pretreatment with the anti-CD13/APN monoclonal antibody F23, which binds with high affinity to the active site of CD13/APN and blocks its enzymatic activity. Moreover, F23 alone was not inhibitory to CD13-positive cells. Furthermore, a similar inhibitory IC50 of actinonin was seen in the CD13-negative cell lines RAJI and DAUDI human lymphoma. These data suggest that the inhibitory effect of actinonin is not mediated by inhibition of CD13/APN. Cell cycle analysis showed that actinonin induces a G1 arrest in HL60 and NB4 cells; apoptosis was observed in 20-35% of the cells as measured by intracellular flow cytometry. To assess whether these effects could be seen in vivo, the effect of actinonin on the syngeneic AKR Mouse leukemia model was evaluated. Actinonin showed dose-dependent antitumor effects on AKR leukemia in vivo, resulting in a survival advantage. In conclusion, apoptosis, growth inhibition, and therapeutic effects in vivo are induced by actinonin and are not likely to be mediated by CD13/APN.
Yang Xu - One of the best experts on this subject based on the ideXlab platform.
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antitumor activity of actinonin in vitro and in vivo
Clinical Cancer Research, 1998Co-Authors: Yang Xu, Janice Gabrilove, David A. ScheinbergAbstract:Actinonin, an antibiotic and CD13/aminopeptidase N (APN) inhibitor, has been shown to be cytotoxic to tumor cell lines in vitro. We investigated the antiproliferative effects of actinonin on human and murine leukemia and lymphoma cells. Actinonin inhibited growth of NB4 and HL60 human cell lines and AKR Mouse leukemia cells in vitro with an IC50 of about 2-5 micrograms/ml. The inhibitory effect on CD13-positive cells was not blocked by pretreatment with the anti-CD13/APN monoclonal antibody F23, which binds with high affinity to the active site of CD13/APN and blocks its enzymatic activity. Moreover, F23 alone was not inhibitory to CD13-positive cells. Furthermore, a similar inhibitory IC50 of actinonin was seen in the CD13-negative cell lines RAJI and DAUDI human lymphoma. These data suggest that the inhibitory effect of actinonin is not mediated by inhibition of CD13/APN. Cell cycle analysis showed that actinonin induces a G1 arrest in HL60 and NB4 cells; apoptosis was observed in 20-35% of the cells as measured by intracellular flow cytometry. To assess whether these effects could be seen in vivo, the effect of actinonin on the syngeneic AKR Mouse leukemia model was evaluated. Actinonin showed dose-dependent antitumor effects on AKR leukemia in vivo, resulting in a survival advantage. In conclusion, apoptosis, growth inhibition, and therapeutic effects in vivo are induced by actinonin and are not likely to be mediated by CD13/APN.
B J Shannon - One of the best experts on this subject based on the ideXlab platform.
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reconstitution of a deficiency of AKR Mouse macrophages for their response to lipid a activation for tumor cytotoxicity by complement subcomponent c1q role of ifn gamma
Journal of Immunology, 1991Co-Authors: R W Leu, Anqiang Zhou, J Rummage, David J Fast, B J ShannonAbstract:C5-deficient AKR Mouse macrophages were initially found to be refractory to activation by lipid A to mediate tumor cytotoxicity for P815 mastocytoma or L1210 Mouse leukemia targets as compared with responsive C3H Mouse macrophages. The lower level of tumor cytotoxicity by lipid A-activated AKR macrophages correlated with lower levels of cytotoxic nitric oxide generation as measured by nitrite end product accumulation. The refractory state of AKR macrophages was unexpectedly found to be independent of their C5 deficiency in that IFN-gamma reconstituted their response to activation by lipid A coincident with an increase in C1q mRNA synthesis. AKR macrophages were augmented in their lipid A activation by exogenous soluble C1q in the absence of IFN-gamma, which corresponded with an increased production of nitric oxide by C1q-reconstituted macrophages. In contrast, responsive C3H Mouse macrophages with sufficient levels of C1q synthesis were inhibited by exogenous soluble monomeric C1q in their lipid A activation. Both AKR and C3H macrophages plated over immobilized C1q were inhibited in their lipid A activation for tumor cytotoxicity and nitric oxide generation. Our results provide evidence that C1q modulates macrophage activation by lipid A for nitric oxide-mediated tumor cytotoxicity under the influence of IFN-gamma, which stimulates C1q synthesis and secretion. These findings strongly suggest that macrophage synthesis of C1q, but not C5, is a prerequisite for their activation by lipid A.
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exogenous c1q reconstitutes a secondary deficiency of c5 deficient AKR Mouse macrophages for fcr dependent cellular cytotoxicity and phagocytosis
Journal of Immunology, 1991Co-Authors: R W Leu, Anqiang Zhou, M J Kennedy, B J ShannonAbstract:Studies originally designed to assess the putative role of endogenous C5 in macrophage activation for antibody-dependent cellular cytotoxicity (ADCC) yielded unanticipated results. Resident and inflammatory peritoneal macrophages from C5-deficient AKR mice were found to have significantly lower capacity for FcR-dependent ADCC activation and phagocytosis of IgG-opsonized SRBC targets than did C5-competent C3HeB/FeJ (C3H) mice. Reconstitution of the ADCC response of AKR macrophages was accomplished initially with C5-sufficient C3H Mouse serum, which suggested that endogenous C5 may be required for ADCC activation. However, further investigation largely eliminated C5 involvement in that a heat-labile component of C5-deficient AKR serum was shown to be active in the reconstitution of ADCC activation of AKR macrophages. Macrophages from AKR mice were found to have significantly lower levels of C1q mRNA synthesis, endogenous C1q levels, and C1q secretion than did C3H Mouse macrophages as determined by Northern blot, Western blot, and presynthetic radiolabeling analysis, respectively. The addition of purified exogenous C1q to IgG-opsonized SRBC targets fully reconstituted ADCC activation for AKR inflammatory peritoneal macrophages to levels of normally FcR-responsive C3H macrophages. Similarly, exogenous C1q augmented FcR-dependent phagocytosis of AKR macrophages but had no effect on macrophages from responsive C3H mice. Our results indicate that AKR mice have a deficiency for FcR-dependent cellular cytotoxicity and phagocytosis that is related to their low potential for C1q synthesis and secretion rather than to their established genetic deficiency for C5 synthesis. We tentatively conclude that endogenous C1q is required as an accessory molecule for macrophage FcR-dependent effector functions and that C5 is not a prerequisite for ADCC activation.
A A Oei - One of the best experts on this subject based on the ideXlab platform.
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promotion of tumor growth by transfecting antisense dna to suppress endogenous h 2kk mhc gene expression in AKR Mouse thymoma
Cellular Immunology, 1991Co-Authors: Kam M Hui, Bee C Sim, Toon Tien Foo, A A OeiAbstract:Many AKR spontaneous thymomas are reported to express different amounts of the major histocompatibility complex class I H-2Kk molecules. Moreover, H-2Kk-deficient AKR tumor cells are found to be more malignant when compared to tumor cells that express abundant levels of the H-2Kk molecules. To corroborate further the role of H-2Kk in tumorigenesis of AKR leukemia, we have, in this study, expressed antisense H-2Kk RNA in a high-H-2Kk-expressing and poorly tumorigenic AKR thymoma cell line 369. The down-regulation of H-2Kk molecules in the transfected 369 clones rendered them more tumorigenic in syngeneic AKR/J mice. The increase in oncogenicity correlates well with a concomitant reduction in their susceptibility to tumor-specific cytotoxic T lymphocytes in vitro. These results suggest the relevance of H-2Kk molecules in the immune surveillance of AKR tumors.