Update: new CD antigens, 1996.
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Antigens, CD↗
Biomedical subjects
M Miyasaka
Publications and source records attributed to M Miyasaka.
Primary human immunodeficiency virus type 1 viremia and central nervous system invasion in a novel hu-PBL-immunodeficient mouse strain.
We established four new mouse strains with defective T and B cells as well as defects in innate immunological reactions using an NK cell depletion antibody and showed that all mutant mouse strains efficiently received human peripheral blood leukocyte (PBL) engraftment (hu-PBL-scid mice). Higher levels of human immunodeficiency virus type 1 (HIV-1) replication were observed in these new hu-PBL-scid mice than in conventional hu-PBL-C.B-17-scid mice. In one particular strain, hu-PBL-NOD-scid mice, high levels of HIV-1 viremia (more than 10(6) 50% infectious doses per ml) were detected after infection with HIV-1. The plasma viral load was about 100 to 1,000 times higher than that observed in other hu-PBL-scid mice infected with HIV-1. Although high-level viremia did not correlate with the total amount of HIV-1 RNA in cells from infected mice, high levels of free virions were detected only in hu-PBL-NOD-scid mice. HIV-1 viremia induced systemic HIV-1 infection involving the liver, lungs, and brain. PCR in situ hybridization confirmed that HIV-1-infected cells invaded the brain tissue of the hu-PBL-NOD-scid mice. Our results suggest that the genetic background, including innate immunity, is critical in the development of primary HIV-1 viremia and subsequent central nervous system invasion with HIV-1. The hu-PBL-NOD-scid mouse represents a useful model for the study of the pathogenesis of HIV-1 in vivo, especially brain involvement, and therapy of primary HIV-1 viremia.
Animals↗
Constitutive expression of ICAM-1 in rat microvascular systems analyzed by laser confocal microscopy.
The present study aimed to demonstrate constitutive expression of the intercellular adhesion molecule (ICAM)-1 among arterioles, capillaries, and venules in the mesentery and liver and to examine the interaction between cultured endothelial cells and leukocytes in rats. ICAM-1 expression in the microvessels in vivo was visually demonstrated by laser confocal fluorescence microscopy. A monoclonal antibody against rat ICAM-1 (1A29) was labeled with fluorescein isothiocyanate, and the binding ratio between the fluorescence and immunoglobulin was determined for data calibration. Intravascularly administered fluorescein isothiocyanate-labeled 1A29 was distributed heterogeneously among the hierarchy of microvessels in the mesentery: postcapillary venules were the major portion expressing ICAM-1 constitutively, and the density of 1A29 bound to their endothelium was at least 10 times higher than that in true capillaries and arterioles in the same mesentery. On the other hand, the liver expressed ICAM-1 abundantly in sinusoids to the extent similar to that in central venules. These results suggest that postcapillary venules serve as an active gateway with the readiness to help adhere circulating leukocytes exposed to proinflammatory stimuli in acute inflammation.
Animals↗
Reperfusion-induced leukocyte adhesion and vascular protein leakage in normal and hypercholesterolemic rats.
The objective of this study was to define the influence of hypercholesterolemia on ischemia-reperfusion (I/R)-induced leukocyte-endothelial cell adhesion and albumin leakage in rat mesenteric venules. The microvascular alterations normally elicited by I/R (leukocyte adherence and emigration, albumin leakage, and platelet aggregation) were more pronounced in hypercholesterolemic rats (compared with control rats). Monoclonal antibodies against the adhesion glycoproteins CD11/CD18 and intercellular adhesion molecule-1 attenuated the I/R-induced leukocyte adherence and emigration and albumin leakage. Leukocyte adherence, but not albumin leakage, was diminished in animals pretreated with a P-selectin-specific antibody. Platelet aggregation was reduced by antibodies directed against either P-selectin, CD18, or intercellular adhesion molecule-1, as well as a GPIIb-IIIa antagonist. These results indicate that the enhanced reperfusion-induced albumin leakage in hypercholesterolemic rats is dependent on leukocyte-endothelial cell adhesion. Furthermore, P-selectin- and CD11/CD18-dependent heterotypic and GPIIb-IIIa-mediated homotypic platelet aggregation appear to influence the extravasation of both leukocytes and albumin in postischemic venules of hypercholesterolemic rats.
Animals↗
P-selectin and vascular cell adhesion molecule-1 are focally expressed in aortas of hypercholesterolemic rabbits before intimal accumulation of macrophages and T lymphocytes.
The accumulation of monocyte/macrophages and T lymphocytes in arterial intima is a hallmark of early atherogenesis. To investigate the temporal relationships between endothelial expression of adhesion molecules (eg, P-selectin and vascular cell adhesion molecule-1 [VCAM-1]) and intimal accumulation of macrophages and T lymphocytes, immunostaining was performed by using serial frozen sections from intercostal branch points of thoracic aortas of New Zealand White rabbits that had been fed a 0.3% cholesterol diet. After 1 week of cholesterol feeding, neither macrophages nor T lymphocytes were detected, although endothelial expression of P-selectin and VCAM-1 was observed. After 3 weeks, macrophages were detectable in 75% and T lymphocytes were present in 25% of the rabbits. Expression of P-selectin and VCAM-1 was sustained until 10 weeks. Infiltration of T lymphocytes was restricted in areas in which macrophages were accumulated and did not appear to precede macrophage infiltration. E-selectin expression was not detectable before accumulation of mononuclear leukocytes; however, very few endothelial cells covering foam cell lesions expressed E-selectin after 6 weeks. Similar results were obtained in Watanabe heritable hyperlipidemic rabbits aged 1, 2, and 3 months. Taken together, localized expression of P-selectin and VCAM-1 may play a key role in the initial recruitment of macrophages and T lymphocytes in early atherogenesis.
Animals↗
Effects of chronic arterial hypertension on constitutive and induced intercellular adhesion molecule-1 expression in vivo.
Recent reports indicate that bacterial endotoxin (lipopolysaccharide) and cytokines elicit a more profound increase in the surface expression of intercellular adhesion molecule-1 (ICAM-1) in cultured endothelial cells derived from spontaneously hypertensive (SHR) versus normotensive Wistar-Kyoto rats (WKY). Our objective in this study was to characterize and compare in vivo ICAM-1 expression in SHR and WKY under basal conditions and after 5 hours of endothelial cell activation with either lipopolysaccharide (5 mg/kg i.p.) or tumor necrosis factor-alpha (TNF-alpha; 1, 5, and 10 micrograms/kg i.p.). ICAM-1 expression was quantified in different tissues by the double-radiolabeled monoclonal antibody technique. When constitutive (baseline) ICAM-1 expression was corrected for endothelial cell surface area, significantly higher values were noted in SHR than WKY but only in splanchnic organs. Lipopolysaccharide and TNF-alpha elicited significant increases in ICAM-1 expression in all tissues of both WKY and SHR. However, the magnitude of the lipopolysaccharide-induced ICAM-1 upregulation in heart, stomach, skeletal muscle, and brain was significantly lower in SHR than WKY. A similar blunted ICAM-1 upregulation was noted in the stomach of SHR after administration of 5 micrograms/kg TNF-alpha. The differences in induced ICAM-1 expression between SHR and WKY do not appear to be due to differences in endothelial cell surface area or plasma glucocorticoid levels. These results suggest that chronic arterial hypertension results in altered ICAM-1 expression on the endothelium, which may contribute to the abnormal inflammatory responses associated with this disease.
Animals↗
Increased expression of intercellular adhesion molecule-1 (ICAM-1) in diabetic rat glomeruli: glomerular hyperfiltration is a potential mechanism of ICAM-1 upregulation.
Mononuclear cells, including monocytes/macrophages and T-cells, are considered to be involved in the progression of diabetic nephropathy, although the mechanism of their recruitment into diabetic glomeruli is unclear. The intercellular adhesion molecule-1 (ICAM-1) promotes the infiltration of leukocytes into atherosclerotic lesions as well as inflammatory tissues. In the present study, we investigated the expression of ICAM-1 in the glomeruli of streptozotocin-induced diabetic rats. The expression of ICAM-1 was increased significantly during the early stage of diabetes. The number of mononuclear cells, primarily monocytes/macrophages and lymphocytes, was significantly increased in diabetic glomeruli. Mononuclear cell infiltration into diabetic glomeruli was prevented by anti-ICAM-1 monoclonal antibody. Insulin treatment decreased ICAM-1 expression and mononuclear cell infiltration. The ICAM-1 expression on cultured human umbilical vein endothelial cells was not induced under high glucose culture conditions. Glomerular hyperfiltration is a characteristic change in the early stage of diabetic nephropathy. Treatment with aldose reductase inhibitor, which prevented glomerular hyperfiltration without changes in blood glucose levels, decreased ICAM-1 expression and mononuclear cell infiltration. Moreover, we examined the ICAM-1 expression in the glomeruli of the 5/6 nephrectomized rat, which is a model for glomerular hyperfiltration without hyperglycemia. The ICAM-1 expression and infiltration of mononuclear cells was significantly increased in the glomeruli of 5/6 nephrectomized rats. We conclude that ICAM-1 is upregulated and promotes the recruitment of mononuclear cells in diabetic glomeruli. Moreover, glomerular hyperfiltration that occurs in the early stage of diabetic glomeruli may be one of the potential mechanisms of ICAM-1 upregulation in diabetic nephropathy.
Aldehyde Reductase↗
High levels of viremia in hu-PBL-NOD-scid mice with HIV-1 infection.
We studied the compatibility of human lymphocyte engraftment and susceptibility to HIV-1 infection in 2 new immunodeficient mice. NOD/Shi-scid mice were generated by backcrossing of the scid mutation into NOD mice while C57BL/6-RAG2(0/0) were generated by knocking out the RAG-2 gene. Human T lymphocytes were reconstituted in new immunodeficient mouse strains. We found that the new immunodeficient mouse strains accepted human PBL engraftment and HIV-1 infection more efficiently than conventional C.B-17-scid mice. Especially in the hu-PBL-NOD/Shi-scid strain, we reproduced the high levels of HIV-1 viremia comparable to or at significantly higher levels than after HIV-1 primary infection. These results indicate that our hu-PBL-NOD-scid animal is useful for investigations of the activation mechanism in HIV-1 replication in vivo and after primary infection.
Acquired Immunodeficiency Syndrome↗
Augmentation rhinoplasty by subcutaneous midline forehead flap simultaneous with implant removal.
Implant exposure after augmentation rhinoplasty with alloplastic materials is usually associated with some degree of infection, and it is commonplace to remove the implant and wait for several months before re-augmentation. However, some patients cannot accept the resultant deformity after implant removal. We introduced the midline forehead flap for augmentation simultaneous to the removal and obtained favorable results, even when considering the donor site scar on the forehead. We report the surgical technique and two patients treated with this procedure. The advantages and disadvantages of this procedure are also discussed.
Aged↗
Two different hard palate closure techniques in two-stage palatoplasty: effects on velopharyngeal closure and articulation.
Two different hard palate closure techniques, in two-stage palatoplasty, was evaluated in 12 patients. The lip and soft palate were closed at 3 to 7 months of age. The patients were then divided into two groups of six and the hard palate closed at 17 to 23 months of age, either by a vomer flap (VF) with a skin graft (Osada's two-stage palatoplasty) in the VF group, or by the push-back (PB) procedure of the mucoperiosteal flap in the PB group. Velopharyngeal closure (VPC) during a gag reflex before and after hard palate closure, and the articulation of these patients after closure, were evaluated and compared between the two groups. Regarding VPC before hard palate closure, three "Poor" and three "Borderline" outcomes were noted in each group. We conclude that, by introducing the pharyngeal flap, the patients in the VF group obtained good articulation, actually comparable to that in the PB group.
Articulation Disorders↗
Introducing a solid model for reconstructing the severely deformed hand.
We report a case of a 39-year-old man with a severely deformed hand resulting from an injury sustained in a traffic accident at 2 years of age. A Marjolin ulcer appeared on the cicatricial area 3 years ago. After radical surgery for squamous cell carcinoma, we planned to realign the axis of the ulnarly flexed hand. Prior to surgery, we produced a solid model of the bony framework using laser lithography based on 3-D CT digital image data. The solid model furnished us and the patient with precise information on the deformity and allowed us to perform preoperative simulation surgery. By a two-stage wedge-shaped ostectomy at the end of the radius, the ulnarly deviated axis of the hand was realigned from 100 to 30 degrees (approximate) in clinical measurement and the patient was quite satisfied with the resulting function and appearance. However, there are some disadvantages of the laser lithography solid model: the cost is high, the resin material is very hard and difficult to operate on, and the model does not include soft-tissue structures. The development of a model in the future that includes vessels, nerves, and tendons will enable surgeons to transfer more precisely the results of the simulation surgery to the patient in the operating room.
Adult↗
Short term treatment with soluble neuroantigen and anti-CD11a (LFA-1) protects rats against autoimmune encephalomyelitis: treatment abrogates autoimmune disease but not autoimmunity.
Resistance to autoimmune encephalomyelitis was induced by s.c. infusion of myelin basic protein (MBP) in saline in combination with i.p. injections of anti-CD11a (LFA-1) mAbs. This treatment induces resistance to EAE induction, which appears early and persists for at least one month after treatment. Some MBP-CFA-challenged resistant rats showed minimal inflammation in the central nervous system, which was, however, confined to the meninges of the lower spinal cord. Examination of the immune status of MBP-anti-LFA-1 treated rats before encephalitogenic challenge failed to reveal any priming when assessed by Ag driven proliferation and cytokine production by lymphoid cells, and by circulating Ab production. Following challenge of protected rats, lymph node cell proliferation to MBP was unaltered, indicating that reactive cells had not been deleted or energized. Resistance could not be transferred with lymphoid cells from treated rats nor abrogated by cyclophosphamide treatment. In treated rats following challenge, there was a shift in the isotype of anti-MBP Ab produced, from an IgG2a:IgG1 ratio of 2:1 to 1:1, due to an increase in IgG1 production, indicating a possible bias towards a nonpathogenic Th2 CD4+ T cell response. The IgG1 Ab was detected early after challenge suggesting that pretreatment had indeed primed the animals, and had primed them to go down the Th2 pathway following encephalitogenic challenge. The ability to divert immune reactivity from a destructive to a nondestructive response could have important therapeutic implications for autoimmune disease.
Adoptive Transfer↗
Intrathecal administration of antibodies against LFA-1 and against ICAM-1 suppresses experimental allergic encephalomyelitis in rats.
The effects of intracerebroventricular administration of mAbs against LFA-1 and ICAM-1 on both active and passive experimental allergic encephalomyelitis (EAE) in rats were examined. Lewis rats were immunized with guinea pig myelin basic protein (MBP) or MBP 68-86 peptide in complete Freund's adjuvant to induce active EAE, or they were injected with encephalitogenic MBP-reactive lymphocytes for adoptive transferred EAE. LFA-1-specific mAbs and/or ICAM-1-specific mAbs or a control mAb or PBS were injected into the lateral ventricles via implanted needles. Intracerebroventricular administration of the specific mAbs together on Days 0, 2, 4, and 6 or on Days 4, 6, 8, and 10 after immunization almost completely suppressed the clinical signs of the actively induced EAE with reduced numbers of the infiltrating cells and reduced percentages of W3/25(+) and IA-29(+) cells in the central nervous system (CNS) of the rats. Pretreatment with both specific mAbs from 14 to 11 days prior to immunization also exhibited a considerable protective effect. However, daily injection from Day 10 to 13 after immunization did not suppress the clinical signs. In rats with adoptive transferred EAE, daily treatment from Day 0 to Day 4 after cell transfer completely abolished clinical signs of EAE, although comparison of histological findings was not remarkable. In conclusion, intrathecal administration of antibodies against LFA-1 and ICAM-1 may be useful for the treatment of human demyelinating diseases, such as multiple sclerosis.
Adoptive Transfer↗
Novel metastasis model of human lung cancer in SCID mice depleted of NK cells.
Metastasis is a critical problem in the treatment of human lung cancer. Thus, a suitable animal model of metastasis of human lung cancer is required for in vivo biological and preclinical studies. In this study, we tried to establish a suitable model for this, using SCID mice. Neither human SCLC H69/VP cells (5 x 10(6)) nor squamous-cell carcinoma RERF-LC-AI cells (1 x 10(6)), injected through a tail vein, formed metastases in untreated SCID mice. Pre-treatment of SCID mice with anti-asialo GM1 serum resulted in only a few metastases of H69/VP cells, but pre-treatment with anti-mouse IL-2 receptor beta chain Ab (TM-beta 1) resulted in numerous lymph-node metastases 56 days after tumor inoculation. H69/VP-M cells, an in vivo-selected variant line, formed significant numbers of lymph-node metastases even in SCID mice pre-treated with anti-asialo GM1 serum. SCID mice depleted of NK cells by treatment with TM-beta 1 showed different patterns of metastasis when inoculated intravenously with the 2 different human lung cancer cell lines (H69/VP and RERF-LC-AI cells): H69/VP cells formed metastases mainly in systemic lymph nodes and the liver, whereas RERF-LC-AI cells formed metastases mainly in the liver and kidneys, with only a few in lymph nodes. A histopathological study showed that the metastatic colonies consisted of cancer cells. The numbers of metastatic colonies formed by the 2 cell lines increased with the number of cells inoculated. TM-beta 1 treatment of SCID mice efficiently removed NK cells from peripheral blood for at least 6 weeks, whereas, after treatment of the mice with anti-asialo GM1 serum, NK cells were recovered within 9 days. These findings suggest that NK-cell-depleted SCID mice may be useful as a model in biological and pre-clinical studies on metastasis of human lung cancer.
Animals↗
Induction of persistent allograft tolerance in the rat by combined treatment with anti-leukocyte function-associated antigen-1 and anti-intercellular adhesion molecule-1 monoclonal antibodies, donor-specific transfusion, and FK506.
We previously reported that a short course of treatment with anti-LFA-1 and anti-ICAM-1 monoclonal antibodies (mAbs) led to a persistent acceptance of mouse cardiac allografts, which resulted from the induction of allospecific tolerance. In the present study, we tested the effect of anti-LFA-1 and anti-ICAM-1 mAbs on rat allograft rejection and analyzed the mechanisms underlying allograft tolerance. In sharp contrast to the mouse case, a short course of treatment with anti-LFA-1 and anti-ICAM-1 mAbs led to a persistent acceptance in only half of the treated rats when MHC was compatible but mismatched for minor antigens, and was virtually ineffective when MHC was fully incompatible. However, treatment with these mAbs combined with donor-specific transfusion and FK506 consistently led to a persistent acceptance, even when the MHC was fully incompatible. Donor-specific tolerance was induced by this treatment, as estimated by skin challenging. In the tolerant rats, proliferative response and CTL generation against donor-type alloantigen were severely impaired but partially restored by exogenous interleukin-2. Limiting dilution analysis demonstrated that the precursor frequency of CTL was decreased in the tolerant rats, as compared with the naive rats. These results suggest that donor-reactive T cells were partially deleted and rendered anergic in the periphery.
Animals↗
Requirement and role of C5a in acute lung inflammatory injury in rats.
The complement activation product, C5a, may play a key role in the acute inflammatory response. Polyclonal antibody to rat C5a was used to define the requirements for C5a in neutrophil-dependent inflammatory lung injury after systemic activation of complement by cobra venom factor (CVF) or after intrapulmonary deposition of IgG immune complexes. In the CVF model, intravenous infusion (but not intratracheal instillation) of anti-C5a produced a dose-dependent reduction in lung permeability and in lung content of myeloperoxidase. In C6-deficient rats, CVF infusion caused the same level of lung injury (measured by leak of 125I-albumin) as found in C6-sufficient rats. In the IgG immune complex model of lung injury, anti-C5a administered intratracheally (but not intravenously) reduced in a dose-dependent manner both the increase in lung vascular permeability as well as the buildup of lung myeloperoxidase. Treatment with anti-C5a greatly suppressed upregulation of lung vascular intercellular adhesion molecule-1 (ICAM-1). This was correlated with a substantial drop in levels of TNFalpha in bronchoalveolar fluids. These data demonstrate the requirement for C5a in the two models of injury. In the IgG immune complex model, C5a is required for the full production of TNFalpha and the corresponding upregulation of lung vascular ICAM-1.
Animals↗
Cell adhesion via murine alpha4 human beta1 integrin chimera on transfected K562 cells to endothelial cells.
To evaluate the property of binding activity of alpha4beta1 integrin in cell-cell interaction, we newly established a cell line, alpha4mK562, by transfecting cDNA of murine integrin alpha4 subunit into human erythroleukemic K562 cells. alpha4mK562 transfectant expressed both murine alpha4 and human beta1 subunit, which generated a functional heterodimer. alpha4mK562 cells more efficiently bound to murine endothelial cell lines and recombinant human TNFalpha (rhTNF)-treated human umbilical vein endothelial cells (HUVEC) than the parental K562 cells. These adhesion resulted from the interaction between alpha4beta1 and VCAM-1. Interestingly, treatment with mAb against human beta1 (4B4 clone), which has been known as inhibitory mAb, enhanced binding of alpha4mK562 cells to rhTNF-treated HUVEC but not to murine endothelial cells. This increase in binding induced by 4B4 mAb was completely inhibited by another mAb against human beta1 (mAb13), but only partially by anti-alpha4 mAb (PSsolidus2). The increase in binding induced by 4B4 mAb was also abolished by metabolic inhibitors, indicating that the increased binding is energy dependent. These observations suggest that the binding of 4B4 mAb to the chimeric alpha4beta1 induces an unique outside-in signaling and enhances the specific binding of alpha4mK562 cells to rhTNF-treated HUVEC.
Animals↗
Restoration of immune abnormalities in diabetic BB rats after pancreas transplantation. I. Macrochimerism of donor-graft-derived RT6+ T cells responsible for restoration of immune responsiveness and suppression of autoimmune reaction.
Diabetes-prone (DP) BB rats (RT1(u), RT6.1) spontaneously develop insulin-dependent diabetes mellitus (IDDM) and the disease manifestation resembles that in human IDDM. DP rats are immunodeficient with severe T lymphocytopenia due to the absence of T cells expressing the RT6 differential alloantigen, which have immunoregulatory functions. MHC- and non-MHC-compatible Wistar Furth (WF; RT1(u), RT6.2) pancreases were transplanted into DP rats. WF pancreas grafts were destroyed by IDDM recurrence (insulitis), but not by rejection, with a mean survival time of 65.3 +/- 21.7 days. To prevent the recurrence of IDDM in the grafts, monoclonal antibodies to intercellular adhesion molecule-1 and leukocyte function-associated antigen-1 were administered. WF pancreas grafts were indefinitely accepted (>108.0 +/- 26.8 days) in monoclonal antibody-treated DP recipients. The number of T cells was increased and cellular immune responses restored only in the DP rats that had accepted grafts. The increased number of T cells was due to the peripheral appearance of donor-type RT6.2+ T cells, which represented 34.3 +/- 7.0% of total splenic T cells. The cytotoxicity of splenic T cells to WF islet cells was suppressed in the presence of RT6+ T cells in vitro. These findings demonstrated that stable macrochimerism of donor-derived RT6+ T cells could restore the immune responses and prevent the recurrence of IDDM in the DP recipients.
ADP Ribose Transferases↗