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Peptides derived from ICAM-1 and LFA-1 modulate T cell adhesion and immune function in a mixed lymphocyte culture. 总被引:7,自引:0,他引:7
S A Tibbetts C Chirathaworn M Nakashima D S Jois T J Siahaan M A Chan S H Benedict 《Transplantation》1999,68(5):685-692
BACKGROUND: The counter receptors intercellular adhesion molecule (ICAM)-1 and lymphocyte function-associated antigen (LFA)-1 are lymphocyte cell surface adhesion proteins the interaction of which can provide signals for T cell activation. This binding event is important in T cell function, migration, and general immune system regulation. The ability to inhibit this interaction with monoclonal antibodies has proved to be therapeutically useful for several allograft rejection and autoimmune disease models. METHODS: Short peptides representing counter-receptor contact domains of LFA-1 and ICAM-1 were examined for their ability to inhibit T cell adhesion and T cell function. RESULTS: Peptides encompassing amino acids Q1-C21 and D26-K50 of ICAM-1, I237-I261 and G441-G466 of the LFA-1 alpha-subunit, and D134-Q159 of the LFA-1 beta-subunit inhibited LFA-1/ICAM-1-dependent adhesion in a phorbol-12,13-dibutyrate-induced model of tonsil T cell homotypic adhesion. This inhibition was specific to the peptide sequence and occurred without stimulation of T cell proliferation. The peptides also were effective in preventing T cell function using a one-way mixed lymphocyte reaction model for bone marrow transplantation. CONCLUSIONS: Our data suggest that these peptides or their derivatives may be useful as therapeutic modulators of LFA-1/ICAM-1 interaction during organ transplants. 相似文献
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Antibodies to both ICAM-1 and LFA-1 do not protect the kidney against toxic (HgCl2) injury 总被引:2,自引:0,他引:2
Ghielli M Verstrepen WA De Greef KE Helbert MH Ysebaert DK Nouwen EJ De Broe ME 《Kidney international》2000,58(3):1121-1134
BACKGROUND: The role of inflammatory leukocytes in acute renal failure (ARF) remains controversial and appears largely uninvestigated in toxic (in contrast to ischemic) ARF. METHODS: Female Wistar rats were injected with monoclonal antibodies (mAbs) directed to both the leukocyte function-associated antigen 1 (LFA-1) and the intercellular adhesion molecule 1 (ICAM-1). Doses (6 mg/kg of each mAb) were given 24 hours prior to the induction of acute tubular necrosis (ATN) by mercuric chloride administration (2 mg/kg, subcutaneously, day 0) and subsequently every 48 hours. Control rats similarly received either control antibody (12 mg/kg) or vehicle prior to and following the induction of ATN. Renal function was also measured from male Lewis rats that were similarly treated with anti-adhesion antibodies during exposure to 30 minutes of unilateral renal ischemia. RESULTS: Injected antibodies were demonstrated on peripheral blood leukocytes (flow cytometrical detection of mouse anti-LFA-1) and on endothelium (immunohistochemical staining of mouse anti-ICAM-1) and were measured in serum (enzyme-linked immunosorbent assay). Macrophages and T cells were prominent in the kidney of control treatment rats after HgCl2 injection, but anti-adhesion treatment clearly had prevented their infiltration. Notwithstanding, renal tubular injury was equally pronounced in all mercuric chloride treatment groups and so was the decline in renal function (serum creatinine, proteinuria). Tubular epithelial cell proliferation seemed slightly less pronounced and delayed in anti-adhesion treated rats. Kidneys from ischemia exposed rats were, however, functionally protected by identical anti-ICAM-1/anti-LFA-1 treatment. CONCLUSION: Prevention of cellular infiltration by mAbs to LFA-1 and ICAM-1 has no effect on renal morphology, function, or regeneration following mercuric chloride-induced ARF in the rat. This result contrasts with the functional protection of the rat kidney to ischemia/reperfusion injury by virtue of an identical antibody treatment protocol. Resolving that controversy should bring better insight in fundamental processes underlying different types of ARF, and will be the subject of further study. 相似文献
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Biological effects of low power laser irradiation on clonal osteoblastic cells (MC3T3-E1) 总被引:1,自引:0,他引:1
K Yamada 《Nippon Seikeigeka Gakkai zasshi》1991,65(9):787-799
Cultured osteoblastic cells were studied to determine the effects of laser irradiation on their rates of proliferation, differentiation, and calcification. A continuous wave Helium-Neon laser with a wavelength of 632.8 nm was used for this study. Clonal osteoblastic cells (MC3T3-E1) were exposed to laser beam at various energy densities. The cell growth rate and DNA synthesis were increased by laser irradiation only in the growing phase of culture. During long-term culture, 45Ca accumulation was enhanced by laser irradiation at 1.0 J/cm2, with four sessions of irradiation resulting in a 46% increase over controls. In contrast, no significant increase in alkaline phosphatase activity was produced by laser irradiation. Electron microscopy revealed a tendency of enlargement of the Golgi apparatus in the laser-treated cells. These results suggest that laser irradiation photoactivates osteoblastic cells, accelerates osteoblastic cell growth and calcification in vitro, and therefore, may promote bone regeneration. 相似文献
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We examined the role of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) during the activation of peripheral blood mononuclear cells (PBMCs) by the human renal carcinoma cell line CaKi-1. ICAM-1 antigen expression was induced on CaKi-1 cells by incubation with either phorbol-12-myristate 13 acetate (PMA) or interferongamma (IFN-). Following a thorough washout of PMA and IFN- and subsequent paraformaldehyde fixation, CaKi-1 cell monolayers were cocultered with allogenic PBMCs. While PMA-treated CaKi-1 cells induced PBMC proliferation and interleukin-2 receptor antigen expression, this was not the case for control of IFN--treated CaKi-1 cells. Furthermore, the induced PBMC proliferation was inhibited by specific monoclonal antibodies against ICAM-1 and LFA-1. Finally, although PMA induced human leukocyte antigen (HLA)-A, B, C antigen expression on CaKi-1 cells, a monoclonal anti-body against this antigen did not inhibit PBMC proliferation. We conclude that PMA can modulate CaKi-1 cells to stimulate allogenic PBMC proliferation in an ICAM-1/LFA-1 dependent, but HLA-A, B, C-independent, fashion. This stimulation might reside in the long-term activation of protein kinase C, induced by PMA. 相似文献
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Thymus lymphocytes activated in vitro by a T cell mitogen (concanavalin A (Con A)) did not form Fc rosettes nor were they cytotoxic against untreated or antiserum-coated target cells. Con A activated spleen cells were cytotoxic against target cells, but they did not display an increased cytotoxic effect against antibody-coated YAC targets, when compared to normal spleen cells. Con A-activated spleen cells as well as cells activated by a mixed lymphocyte culture did not form Fc rosettes. Thus, activated cytotoxic T cells did not form Fc rosettes nor did they cause cytotoxicity on antibody-coated target cells. Antibody coating of the target cells did not suppress expression of cytotoxicity of activated T cells. 相似文献
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BACKGROUND: Intercellular adhesion molecule (ICAM-1) is important in leukocyte adhesion-dependent events and some data suggest that ICAM-1 provides T cell costimulation. We anlayzed the role of the ICAM-1 and leukocyte function associated antigen-1 (LFA-1) interaction in human T cell alloreactivity in vitro. METHODS: Allo-antigen-induced T cell proliferation and cytotoxic T lymphocyte lytic activity were assessed by mixed lymphocyte reaction assay and 51 Chromium release assay, respectively. Immunostaining and flow cytometry were used to assess the expression of receptors on activated T cells. RESULTS: Alloantigen-induced T cell proliferation and cytotoxic T lymphocyte activity were markedly inhibited by antibodies to ICAM-1 and LFA-1. These antibodies had to be present at the time of initial T cell receptor/antigen engagement to inhibit proliferation. Neither IL-2 nor IL-4 were involved in the observed inhibition by antibodies. Inhibition was not associated with altered cell surface expression of receptors such as CD3, CD4, ICAM-1, LFA-1, CD25, and HLA-DR however, these antibodies did impede the ability of generation of functionally active T cells. Interestingly, these antibodies inhibited soluble, but not immobilized OKT3-induced proliferation of peripheral blood leukocytes. Antibody-mediated inhibition of proliferation failed to impair the ability of T cells to subsequently proliferate in response to stimulation by the original or third party alloantigen or mobilize [Ca++]i in response to CD3 or LFA-1 receptor ligation. CONCLUSIONS: These data demonstrate that blockade of ICAM-1/LFA-1 binding at the time of allorecognition potently blocks initial T cell effector functions that could be due to lack of effective T cell/APC engagement. 相似文献
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Blocking of cytotoxic T cell function by monoclonal antibodies against the CD45 antigen (T200/leukocyte-common antigen) 总被引:1,自引:0,他引:1
Cytotoxic T cells are important effectors in graft rejection and antiviral immunity. A full identification of the functional surface molecules used by these cells may help in determining the best strategies for the therapeutic control of rejection responses. Many T cell surface molecules have been implicated in cytotoxic function through the ability of specific monoclonal antibodies to inhibit T cell activity in vitro. Such measures of "inhibition" must be affected by the avidity of interaction of antibody with the particular surface molecule, as well as the avidity of that surface molecule for any physiological ligand. We show that the introduction of an antiglobulin step substantially amplifies the inhibitory effects of certain CD3 and CD8 monoclonal antibodies, presumably by conferring multivalency. In addition the "antiglobulin" approach has permitted, for the first time, the demonstration that monoclonal antibodies to the "common" determinants of the leukocyte-common antigen family (CD45/LCA/T200) prevent cytotoxic T cell function. 相似文献
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H Tsujihashi H Ishihara A Nakanishi H Matsuda S Uejima T Akiyama T Kurita 《Nihon Hinyōkika Gakkai zasshi. The japanese journal of urology》1989,80(2):204-209
The effect of lymphokine-activated killer (LAK) cells on bladder tumor was examined in vivo and in vitro. In the in vitro experiment, 51Cr-cytotoxic assay was performed for which PBL were used as effector cells. A LAK activity of 26.6% was observed in PBL cultured with IL2 for 4 days, whereas OK-432-induced LAK activity was 22%. Furthermore, in the in vivo experiment, the anti-tumor effect of LAK cells was evaluated in human bladder tumor transplanted into nude mouse. IL2, OK432-induced LAK cells were injected intratumorally. In the LAK-treated group, inhibition of tumor growth was seen. Histologically, it was demonstrated that infiltrating lymphocytes were scattered around tumor cells. The augmentation of NK activity in spleen cells was observed in the LAK-treated group. Although further studies are required to establish its full significance, these findings suggest that immunotherapy against bladder tumors is hopeful. 相似文献
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The "well encapsulated" pleomorphic adenoma has at best a pseudocapsule which allows for bits of satellite tumor to be left behind at "enucleation" surgery as well as for easy "spillage" of tumor by the overconfident surgeon. Recurrent pleomorphic adenomas then become difficult tumors to eradicate and place vital structures, such as the facial nerve, in jeopardy. 相似文献
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S Shibata M Fukushima M Inoue K Tsutsumi K Mori 《No shinkei geka. Neurological surgery》1985,13(3):275-281
In order to elucidate pathogenesis of perifocal edema in the human brain tumors, we observed the alteration of capillary permeability between the glioblastomas with remarkable edema (4 cases) and astrocytoma with slight edema (3 cases). Specimens were studied by conventional ultrathin section and freeze-fracture replica technique. In ultrathin sections of capillaries in glioblastomas, some of these cell junctions were tortuous, elongated, in fact, open. Other capillary abnormalities included endothelial hyperplasia with extensive vesicular formation, surface infolding of endothelial cells, irregularity of the basal lamina and the presence of a large collagen filled extracellular space. In freeze-fracture replicas of capillary endothelium, pinocytotic vesicles markedly increased and were an average fo 52 per micron. Tight junction in one area was seen as network of 6 strands composed of about 100A particles, but in the other areas as one or two strands. In ultrathin sections of astrocytoma, yet there were blood vessels appeared relatively normal. In freeze-fracture replicas, pinocytotic vesicles markedly increased and were an average of 34 per micron. Tight junction was seen as network of 7 strands. We concluded that fewer strands of the tight junction play an important role in increasing the permeability in the vessels of glioblastomas with severe perifocal edema, in addition to increasing the pinocytotic vesicles. 相似文献