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Biomedical subjects

S Izui

Publications and source records attributed to S Izui.

At least 163 records · Page 9Linked to original sources
PubMed1984

Induction of various autoantibodies by mutant gene lpr in several strains of mice.

The effect of the autosomal mutant gene lpr (lymphoproliferation) on the development of various autoantibodies and immune complex (IC) glomerulonephritis was investigated in four genetically distinct strains of mice: MRL/ MpJ , C3H/HeJ, C57BL/6J, and AKR/J. The presence of the lpr gene not only enhanced the production of autoantibodies in the autoimmune MRL/ MpJ strain, but also induced the formation of various kinds of autoantibodies in the three other strains of mice without any apparent predisposition to autoimmune disease. Autoantibodies induced by the lpr gene included anti-double-stranded DNA, anti-single-stranded DNA, anti-IgG, anti-thymocyte, and anti-serum glycoprotein gp70. This indicates that the action of the lpr gene on the development of autoantibody response does not require the particular abnormalities of the MRL genome. The differences in amounts and types of autoantibodies among the lpr strains reflect the difference in the background genome of each strain, suggesting the participation of other genes or factors determining the quantity and/or specificity of autoantibodies. In addition to the development of autoantibodies, the three nonautoimmune strains of mice produced high levels of unidentified IC in the presence of the lpr gene, detectable by the C1q and the conglutinin binding tests. Their glomerular lesions, however, were relatively limited when compared with MRL/ MpJ -lpr/lpr mice, which developed severe glomerulonephritis early in their life. These results suggest that the lpr gene is able to induce the formation of various autoantibodies and IC at significant concentrations in nonautoimmune mice, but for the full manifestation of systemic lupus erythematosus there may be a requirement for supplemental genetic abnormalities or factors.

Animals↗
PubMed1984

Acute SLE in F1 hybrids between SB/Le and NZW mice; prominently enhanced formation of gp70 immune complexes by a Y chromosome-associated factor from SB/Le mice.

Both sexes of the F1 hybrids between SB/Le and NZW mice developed a spontaneous lupus-like disease. Their disease is essentially identical in time course and nature with autoimmune responses that are seen in the F1 hybrids between BXSB and NZW mice. The presence of abnormal Y chromosomes in the SB/Le strain was proved by the finding that the accelerated disease occurred in the F1 hybrid males only when the male parent was SB/Le but not NZW. The acceleration of disease in male F1 hybrids with abnormal Y chromosome was significantly associated with the enhanced formation of gp70 IC but not anti-DNA antibodies. These results indicate that all or almost all of the genetic abnormalities expressed in the BXSB strain are contributed by the SB/Le strain, and the Y chromosome-associated factor enhances the autoimmune response to serum gp70 antigen more markedly than to DNA antigens.

Acute Disease↗
PubMed1984

Association of elevated serum glycoprotein gp70 with increased gp70 immune complex formation and accelerated lupus nephritis in autoimmune male BXSB mice.

BXSB male mice, which spontaneously develop a systemic lupus erythematosus (SLE) like disease, were the only strain to have a significant incidence of abnormally elevated levels of gp70 in sera. Concentrations of gp70 in some mice were more than 10 times (greater than 500 micrograms/ml) those of young BXSB and any other murine strain. The presence of high serum levels of gp70 was significantly associated with hepatic sinusoidal lymphocytosis, a high incidence of which was only observed in male BXSB mice. Serum levels of gp70-anti-gp70 immune complexes were greatly increased in mice with high levels of gp70, presumably associated with increased anti-gp70 antibody production. Such mice developed fatal glomerulonephritis significantly earlier than those with lower levels of gp70. These results suggest that (1) hepatic inflammation of unknown aetiology occurring uniquely in male BXSB mice during the course of their SLE may be responsible for the enhanced expression of serum gp70 antigen, because of its nature as an acute phase reactant and (2) enhanced expression of gp70 antigen is associated with increased formation of anti-gp70 antibodies and exacerbation of lupus nephritis in male BXSB mice.

Animals↗
PubMed1983

Induction of acute thrombocytopenia and infection of megakaryocytes by Rauscher murine leukemia virus reflect the genetic susceptibility to leukemogenesis.

Acute thrombocytopenia and megakaryocyte infection have been investigated during the preleukemic phase of the disease induced by the Rauscher murine leukemia virus (RMuLV) in mice. Injection of RMuLV, either intravenously or intraperitoneally, rapidly induced thrombocytopenia, possibly as a result of direct interaction between platelets and viral particles. The susceptibility to this acute thrombocytopenia was genetically controlled and was inherited as a dominant trait. Murine strains with H-2d or H-2k haplotype, which are susceptible to the induction of leukemia by RMuLV, developed thrombocytopenia, whereas leukemia-resistant H-2b and H-2q strains of mice failed to develop thrombocytopenia. Using B10 H-2-congenic and intra-H-2-recombinant mice, it was shown that the susceptibility to RMuLV-induced thrombocytopenia was controlled by gene(s) in or closely linked to the D region of the H-2 complex. Megakaryocytes may be one of the first sites for the replication of RMuLV. Indeed, among bone marrow cells, only megakaryocytes expressed viral antigens gp70 and p30 during the initial phase of RMuLV infection. In addition, megakaryocytes from infected mice were able to transfer preleukemic thrombocytopenia as well as leukemia in syngeneic mice. The infection of megakaryocytes by RMuLV appears to be genetically controlled in a manner similar to the induction of thrombocytopenia, since only the megakaryocytes from mice developing thrombocytopenia were infected by RMuLV. These results indicate that the gene(s) governing the induction of thrombocytopenia by RMuLV may be the same gene(s) (or closely linked to the gene) that controls the susceptibility to leukemogenesis, and would be consistent with the expression of the gene product, presumably a receptor-like molecule for RMuLV, on platelet and megakaryocyte membranes.

Acute Disease↗
PubMed1983

Induction of murine autoimmune disease by chronic polyclonal B cell activation.

In vivo, prolonged polyclonal activation of B cells by the nonantigenic but potent mitogenic lipid A portion of lipopolysaccharide (LPS-R595) resulted in acceleration of the late life systemic lupus erythematosus disease of female MRL/n, BXSB, and NZW mice, mimicking the time, form, and histopathological features characteristic of their early life disease counterparts, i.e., MRL/l females, BXSB males, and (NZB X NZW)F1 females. Similar polyclonal B cell activation of "immunologically normal" mice has less effect and led to a limited expression of autoimmune disease. This R595-induced autoimmunity and immune complex-mediated disease seemed to be the direct result of activation of the immune system and not from other effects of endotoxin since C3H/HeJ, a strain lacking lymphocyte receptors for LPS-R595, had neither serological nor histological evidence of autoimmune disease despite identical treatment.

Animals↗
PubMed1983

Circulating immune complexes and their possible relevance to other immunological parameters in Guatemalan onchocerciasis.

Circulating immune complexes (CIC) were demonstrated in sera of Guatemalan patients with onchocerciasis by Raji cell radioimmunoassay. 44% of patients but none of controls had abnormally high concentrations of CIC in their sera. The increased concentrations of CIC were found more frequently in patients with lower density of microfilariae in their skin biopsies. Patients with higher concentrations of CIC appeared to have increased titers of serum antibodies to Onchocerca volvulus. A depression of both humoral immune response to tetanus toxoid and delayed hypersensitivity reaction to PPD were found in patients with onchocerciasis. CIC may be involved in modulation of the immune response in onchocerciasis.

Adolescent↗
PubMed1983

Enriched lipid diet accelerates lupus nephritis in NZB x W mice. Synergistic action of immune complexes and lipid in glomerular injury.

The effect of a lipid-rich diet was investigated in autoimmune NZB x W mice with immune complex lupus nephritis. Mice on an enriched lipid diet died sooner than controls. This increase in dietary fat elevated serum cholesterol levels and was associated with an accelerated loss of renal function. Ultrastructural examination of glomeruli revealed lipid in the peripheral loops and mesangium adjacent to immune deposits. Increased lipid accumulation was confirmed by histochemical staining and biochemical extraction. Accelerated disease was not related to changes in immune parameters. Thus, a high lipid consumption accelerated lupus nephritis by a local vascular effect and not by a systemic influence on the immune response. Therefore, in our system, a combined immunologic and lipid glomerular capillary insult caused a more rapidly progressive renal disease than immune complex injury alone.

Animals↗
PubMed1982

Murine serum glycoprotein gp70 behaves as an acute phase reactant.

A single intraperitoneal injection of bacterial lipopolysaccharide (LPS) or its lipid A component induced high levels of glycoprotein, gp70, in sera of several strains of mice within 24 h. This serum gp70 response induced by LPS was independent of the activation of B cells and the presence of T cells. However, serological and immunohistochemical studies demonstrated the production of gp70 by hepatic parenchymal cells and its subsequent release into the circulating blood. The expression of gp70 in the serum was enhanced not only by LPS but also other inducers of acute phase reactants (APR) such as turpentine oil or polyriboinosinic-polyribocytidylic acid. Further, the serum gp70 response was kinetically identical to those of APR. These results strongly suggest that (a) the liver may be the major source for serum gp70, (b) serum gp70 behaves like an APR, (c) its expression may be controlled by a mechanism similar to that for other APR, and (d) this glycoprotein apparently behaves as a normal host constituent and not a product of a viral genome.

Animals↗
PubMed1982

The cellular basis for resistance to induction of tolerance in BXSB SLE male mice.

The autoimmune BXSB male mouse early in life displays a resistance to tolerance induction that is common with the other autoimmune strains (MRL/1, NZB x W, and NZB) whereas its female counterpart, which in early life is immunologically normal, is easily tolerized. The cellular basis for the BXSB male's resistance to tolerance induction with DHGG was investigated by using adoptive male-female cell transfer systems. We found that irradiated female recipients of male T-depleted bone marrow cells, plus either male or female thymus cells, resisted tolerance induction, had hyperactive splenic Ig-secreting cells, and developed early glomerulonephritis. Recipients of male thymic cells plus T-depleted female bone marrow cells could be tolerized, did not have enhanced Ig secretion, and did not develop glomerulonephritis. Furthermore, donor male T-depleted bone marrow cells--but not male thymic, female thymic, or female bone marrow cells--resisted induction of tolerance before their transfer to produce lymphoid chimeras.

Animals↗
PubMed1982

Suppression of transferred BXSB male SLE disease by female spleen cells.

The severe autoimmune disease from which BXSB males die at an early age (young) can be transferred into lethally irradiated female recipients by inoculating them with male spleen or bone marrow cells; similar recipients of female spleen or bone marrow cells develop the late-life disease typical of BXSB females. Using this syngeneic cell transfer model, we investigated the possible ability of female splenic and bone marrow cells to modulate the transferred male disease. We found that female spleen cells or the T-enriched subpopulation of such cells successfully retarded the transferred male disease, as observed by the decreased and delayed glomerulonephritis-associated mortality and lowered levels of serum IgG, autoantibodies, and immune complexes. Transfers of female bone marrow or thymus or female splenic T-depleted subpopulations were incapable of suppressing the accelerated male disease. These results indicate that abnormalities of the male spleen or bone marrow inocula responsible for the transferred early autoimmune disease can be modified by female spleen cells, in particular the female T cell component.

Animals↗
PubMed1981

Low-calorie diet selectively reduces expression of retroviral envelope glycoprotein gp70 in sera of NZB x NZW F1 hybrid mice.

The effect of dietary restriction on the expression of retroviral envelope glycoprotein, gp70, and the formation of gp70-anti gp70 immune complexes was investigated in lupus-prone NZB x NZW F1 hybrid mice. Restricting total calorie intake from the usual 20 to only 10 calories per day after weaning markedly reduced serum levels of both free and antibody-complexed gp70, prevented renal disease, and increased the life spans of these mice. The reduction in serum gp70 was evident after only 2 wk of feeding these animals the low-calorie diet, and the concentration remained virtually unchanged throughout the course of 10 mon experimentation. However, serum concentrations of the major structural protein, p30, of endogenous retroviruses were not altered by restricting calories. Amounts of the serum glycoprotein, haptoglobin, decreased parallel to those of gp70 but amounts of albumin did not. These results suggest that the expression of gp70 in serum is controlled independently of the production of complete viral particles, and regulated by a mechanism similar to that for other serum glycoproteins, such as haptoglobin.

Animals↗
PubMed1981

Retroviral gp70 immune complexes in NZB x NZW F2 mice with murine lupus nephritis.

NZB x NZW (NZB x W) F1 hybrid mice spontaneously develop a disease most prominently characterized by immune complex glomerulonephritis (GN), which seems to be associated with both antibodies to DNA and to the serum retroviral envelope glycoprotein, gp70. To evaluate the contribution of each of these autoimmune responses to the pathogenesis of the GN, we studied NZB x W F2 mice in which the two responses appeared to segregate relatively independently. Use of this model permitted analysis of possible correlations between each response and the G.N. The presence of circulating anti-gp 70-complexed gp70 correlated significantly with the development of fatal GN and one could predict the course of renal disease by computing the rising serum levels of gp70 complexed with antibodies. In contrast, the presence of free antibodies to either double-stranded or single-stranded DNA was not significantly associated with the development of fatal GN. This association of anti-gp70 antibody production with these animals' early death from GN strongly suggests that the gene(s) governing production of antibodies to serum retroviral gp70 may be one of the major genes responsible for spontaneous renal disease segregated in NZB x W F2 generations.

Animals↗
PubMed1981

(NZW x BXSB)F1 hybrid. A model of acute lupus and coronary vascular disease with myocardial infarction.

Both sexes of the (NZW x BXSB)F1 mice developed an early systemic lupus erythematosus-like disease. In males, the disease resembled that in the BXSB male parent and was not affected by sex hormonal manipulation. In females, the disease duplicated that of (NZB x NZW)F1 females by virtue of a delayed onset and estrogen dependence. Autoantibody production, circulating Ig-bound gp 70 immune complexes, and deposition of Ig and gp 70 in the affected glomeruli were demonstrated in both males and females. The abnormally high incidence of degenerative coronary vascular disease with myocardial infarction, particularly in these F1 males, provides a useful model for the investigation of a possible immunologic component in coronary vascular disease.

Acute Disease↗