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Biomedical subjects

S Izui

Publications and source records attributed to S Izui.

At least 181 records · Page 10Linked to original sources
PubMed1981

Identification of retroviral gp70 and anti-gp70 antibodies involved in circulating immune complexes in NZB X NZW mice.

Retroviral gp70 and anti-gp70 antibodies were isolated from circulating immune complexes (IC) of 7-10-mo-old (NZB X NZW)F1 mice, after which the nature and origin of this gp70 (IC-gp70) and the immunologic characteristics of these anti-gp70 antibodies (IC-anti-gp70) were investigated. Immunochemical and structural analyses of IC-gp70 demonstrated that among multiple immunologically related gp70 expressed in all mice, the IC-gp70 had characteristics similar to those of NZB xenotropic viral gp70 (NZB-X1 gp70) that is commonly present in sera of virtually all strains of mice. The study of binding by IC-anti-gp70 antibodies to retroviral gp70 from various sources showed that the IC-anti-gp70 were primarily directed to NZB-X1 gp70 as well as serum gp70. These data strongly suggest that the abnormality of murine strains with systemic lupus erythematosus causing them to produce antibodies to their own xenotropic viral gp70 and to form IC with serum gp70 is not based on their expression of an unusual type of gp70, but rather their ability to make an antibody to NZB-X1 gp70, probably as a result of their immunologic dysfunction.

Animals↗
PubMed1981

Subclass-restricted IgG polyclonal antibody production in mice injected with lipid A-rich lipopolysaccharides.

The effects of five distinct bacterial lipopolysaccharides (LPS) on the induction of polyclonal IgM and IgG antibodies, including polyclonal autoantibody formation, were investigated in several strains of mice. Injections of most LPS preparations that contained polysaccharide transiently induced only IgM polyclonal antibodies. However, LPS from Salmonella minnesota R595 (R595 LPS), which had a particularly high content of lipid A but lacked O-antigen polysaccharide, induced a markedly prolonged IgM and IgG polyclonal antibody response in mice, including athymic nude mice, but not in LPS-unresponsive C3H/HeJ mice. Polyclonal IgM and IgG production peaked in sera on day 8 and day 15, respectively, and remained higher than control values 2 mo after the injection. The IgG induced by R595 LPS was strictly restricted to IgG2b and Igg3 subclasses in normal mice. In contrast, in athymic nude mice which have normally lower levels of IgG1 and IgG2a than normal mice, R595 LPS stimulated the production of all the IgG subclasses and reconstituted serum levels of IgG1 and IgG2a up to, but not higher than, control values of normal mice. These findings suggest that different mechanisms regulate production of each IgG subclass after stimulation with LPS.

Animals↗
PubMed1981

Induction of high serum levels of retroviral env gene products (gp70) in mice by bacterial lipopolysaccharide.

In the present study, mice each given a single intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS) responded with increased serum levels of the major envelope glycoprotein, gp70, of endogenous retrovirus. Concentrations of gp70 in their sera began to increase 4 hr after LPS injection, reached maximal 5- to 15-fold increases after 12--24 hr, and returned to the preinjection levels within 3 days. This response occurred only in the strains characterized by high base line levels of serum gp70 (greater than 10 micrograms/ml) such as NZB, NZB X NZW F1, BXSB, MRL, NZW, DBA/2, LG, 129(GIX+), and C57BL/6(GIX+). However, strains such as DBA/1, C3H/St, BALB/c, C57BL/6(GIX-), and 129(GIX-) with lower base line levels of serum gp70 (less than 5 micrograms/ml) made little or no response. This serum gp70 induced by LPS was structurally similar to the gp70 of NZB xenotropic virus that is dominantly expressed in sera from virtually all strains of mice. However, (i) the induced gp70 was virion-free; (ii) xenotropic virus was not isolatable from BXSB, MRL/1, or 129(GIX+) mice injected with LPS; and (iii) amounts of the major structural viral protein, p30, did not increase correspondingly in sera. All of these findings indicate that the increased expression of serum xenotropic viral gp70 in response to LPS did not result from activation of replication-competent xenotropic virus. In addition, the serum gp70 response to LPS was abolished by simultaneous inoculation of an inhibitor of protein synthesis, D-galactosamine. These results strongly suggest that LPS selectively stimulates synthesis of the env gene product, gp70, of NZB xenotropic virus but other viral gene products.

Animals↗
PubMed1980

Selective suppression of retroviral gp70-anti-gp70 immune complex formation by prostaglandin E1 in murine systemic lupus erythematosus.

The effect of pharmacologic quantities of prostaglandin E1 (PGE) was investigated in three strains of mice (NZB X NZW, MRL/1, and BXSB) that spontaneously develop lupus-like glomerulonephritis. PGE-treatment prolonged survival and retarded the glomerular deposition of immune complex (IC) and the development of glomerulonephritis in NZB X NZW and MRL/1 mice, but did not similarly protect BXSB mice. Changes in the responsive strains correlated well with reduced amounts of circulating gp70 complexed with anti-gp70 antibodies compared with untreated controls, although total concentrations of gp70 (free and complexed) detectable in sera were similar in both groups of mice. The results strongly suggest that: (a) PGE selectively suppressed the immune response to retroviral gp70, (b) PGe had little effect on the quantity or quality of anti-DNA antibodies but did reduce the deposition of anti-DNA containing IC in the kidneys, and (c) gp70 IC appear to play an important role in the pathogenesis of glomerulonephritis in murine systemic lupus erythematosus.

Animals↗
PubMed1980

Effect of lipid A-associated protein and lipid A on the expression of lipopolysaccharide activity. I. Immunological activity.

A detailed investigation has been made of the contribution of the various chemical moieties of bacterial endotoxins, namely lipid A-associated protein (LAP), lipid A and O-antigen polysaccharide to a number of the immunological activities of these active bacterial products. Advantage was taken of the availability of antigenically identical endotoxin preparations from Escherichia coli 0111:B4 which differed greatly in their content of LAP and/or lipid A. The capacity to initiate in vitro proliferative responses in murine splenocytes was in a large part related to the presence of LAP with a less potent, although still critical, dependence upon lipid A. On the other hand, the in vivo polyclonal antibody response was dependent only upon lipid A. In this respect, the presence of LAP had no apparent effect on the stimulation of nonspecific low affinity antibody. All preparations, regardless of LAP and lipid A content, stimulated similar in vivo enhancement of antibody responses to a protein antigen (adjuvanticity) and specific immune responses to the endotoxin polysaccharide antigen. The results emphasize the lack of correlation between in vitro B lymphocyte proliferative responses and in vivo immunostimulatory responses of bacterial endotoxin preparations. These data also suggest a minimal contribution of LAP to in vivo responses and an extremely limited contribution of lipid A to the adjuvant activity and the primary immune response to O-antigen polysaccharide.

Adjuvants, Immunologic↗
PubMed1980

Male determined accelerated autoimmune disease in BXSB mice: transfer by bone marrow and spleen cells.

Autoimmune disease in BXSB mice progresses more rapidly in male animals. We have investigated the cellular basis of this effect by transferring male and female bone marrow and spleen cells into male and female lethally irradiated BXSB recipients. The rate of development of disease was measured by the overall mortality rate, mortality from glomerulonephritis, and development of serologic abnormalities. We found that the pace of disease in the BXSB sex chimeras was determined entirely by the sex of the donor of the transferred cells. Lethally irradiated BXSB animals receiving male cells had rapidly progressive disease, whether the recipients were themselves male or female, whereas female-cell recipients of either sex had slowly progressive disease. The male-specific effect that accelerates autoimmune disease in the BXSB is thus not hormonally mediated, but rather is expressed in the hematopoietic stem cell populations.

Aging↗
PubMed1979

Association of circulating retroviral gp70-anti-gp70 immune complexes with murine systemic lupus erythematosus.

Endogenous retroviral gp70 was investigated as a participant in the pathogenesis of a lupus-like disease that spontaneously develops in four kinds of mice (NZB, NZB x W MRL/1, and male BXSB). Sera from these strains contain a heavy form of gp 70 that varies in sedimentation rates from 9S to 19S in sucrose density gradient analysis and appears with the onset of disease and persists throughout its course. Immunologically normal strains of mice do not develop rapidly sedimenting gp70 by 8-10 mo of life. The fact that the heavy gp70 is selectively absorbed with anti-IgG antibodies or with Staphylococcus aureus protein A suggests that it is complexed with antibodies. The incidence and quantities of these gp70 ICs rise with the progression of disease in all strains with lupus. These findings suggest that Ig-complexed heavy gp70 may be involved in the pathogenesis of glomerulonephritis of mice with SLE.

Animals↗
PubMed1979

Induction of thymocytotoxic autoantibodies after injection of bacterial lipopolysaccharides in mice.

The injection of bacterial lipopolysaccharides (Salmonella typhimurium and Escherichia coli LPS) has been shown to induce thymocytotoxic autoantibodies in various strains of mice (C57BL/6, BALB/c, DBA/2, AKR, A/J and C3HeB/FeJ). Titers up to l:16 were observed. Such antibodies did not develop in C3H/HeJ mice which are low responders to LPS. The thymocytotoxic antibodies had the following characteristics: (a) 2-mercaptoethanol sensitivity, (b) optimal reactivity at 4 degrees C, (c) cytotoxicity for autologous and syngeneic thymocytes but not for spleen cells. The cytotoxicity decreased after absorption with thymocytes, spleen cells or brain tissue but not with kidney or liver homogenates. These LPS-induced thymocytotoxic antibodies were similar to the natural thymocytotoxic antibody occurring in NZB mice.

Animals↗
PubMed1979

Relevance of polyclonal antibody formation to the development of autoimmunity : the model of African trypanosomiasis.

There is an induction of anti-DNA antibodies in mice following the administration of bacterial lipopolysaccharides, Dextran sulfate and PPD, which is closely associated with the property of these substances to trigger a polyclonal B cell activation. In the experiments model of African trypanosomiasis there is also an intense polyclonal antibody synthesis paralleled by the formation of several autoantibodies: anti-DNA, anti-bromelain treated mouse red blood cells and antithymocyte antibodies.

Animals↗
PubMed1979

Effect of prostaglandin E on immune complex nephritis in NZB/W mice.

Pharmacologic quantities of prostaglandin alter the immune complex nephritis of NZB/W mice. To study the mechanism of this change, NZB/W mice received 200 micrograms. of prostaglandin E1 or E2 twice daily starting at 2, 4, or 6 months of age. Mice were sacrificed at bimonthy intervals, renal function and serologic parameters were evaluated, and renal tissue was examined by light, fluorescence, and electron microscopy. Therapy decreased the incidence of proteinuria, lessened renal pathology, and prolonged survival. Maximal beneficial effects occurred when treatment began at 2 months of age. The most striking change was a decrease in the rate of immune complexes depositing in the mesangium and their absence from peripheral loops. Accompanying this change was a reduction in glomerular hypercellularity and a decrease in renal perivascular and interstitial mononuclear infiltrates. By contrast, treatment did not alter serum levels of immunoglobulins, antinuclear antibodies, and antisingle or double-stranded DNA. These results indicate that prostaglandin E is capable of prolonging survival in NZB/W mice by decreasing the rate of immune complexes depositing in glomeruli.

Animals↗
PubMed1979

IgM rheumatoid factors in mice injected with bacterial lipopolysaccharides.

Bacterial lipopolysaccharides (LPS) induced the formation of IgM rheumatoid factors (RF) in several strains of mice including athymic C57BL/6 nude mice, but not in the LPS-resistant C3H/HeJ mice. The RF induced by LPS reacted not only with murine IgG but also with IgG from cows, goats, guinea pigs, and humans. The kinetics of this RF response to injection of LPS were similar to those of antibody response against DNA and a hapten, dinitrophenyl (DNP), and to those of total IgM production. In addition, the RF activity of individual serum samples correlated significantly with levels of anti-DNA and anti-DNP antibodies and of IgM. Therefore, it is concluded that the induction of RF results from polyclonal antibody synthesis by B cells stimulated with LPS. This observation suggests that LPS or LPS-like substances may help to generate RF in patients with rheumatoid arthritis or with some infectious diseases.

Animals↗
PubMed1978

Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains.

MRL/1 and BXSB male mice have a systemic lupus erythematosus (SLE)-like disease similar to but more acute than that occurring in NZB X W mice. The common elements of lymphoid hyperplasia, B-cell hyperactivity, autoantibodies, circulating immune complex (IC), complement consumption, IC glomerulonephritis with gp70 deposition, and thymic atrophy were found in all three kinds of SLE mice. On the basis of these common elements, SLE seen in these mice can be considered a single disease in the same sense that human SLE is one disease. The differences in the SLE expressed in the different mice are no greater than those found in an unselected series of humans with SLE. However, the significant quantitative and qualitative variations in abnormal immunologic expression suggest that different constellations of factors, genetic and/or pathophysiologic, may operate in the three murine strains and that each constellation is capable of leading, via its particular abnormal immunologic consequences, to the activation of common immunopathologic effector mechanisms that cause quite similar SLE-like syndromes. From an experimental point of view, the availability of several inbred murine strains of commonplace histocompatibility types that express an SLE-like syndrome makes possible innumerable manipulations which should help to elucidate the nature and cause(s) of this disorder.

Animals↗
PubMed1978

The spontaneous development of thymocytotoxic antibodies in athymic nude mice and its suppression after transfer of syngeneic thymocytes.

Athymic nude mice early in life spontaneously develop a high level of thymocytotoxic antibodies which have characteristics similar to the thymocytotoxic autoantibodies occurring in young NZB mice. Thymocytotoxic activity was no longer detectable in the serum of nude mice two weeks after the intravenous injection of syngeneic thymocytes, although the levels of spontaneously occurring anti-DNA and anti-hapten antibodies were not affected by the cell transfer.

Animals↗