Biomedical subjects

E Montecino-Rodriguez

Publications and source records attributed to E Montecino-Rodriguez.

27 records · Page 2Linked to original sources

PubMed1992

Serum immunoglobulin isotype profile of viable and non viable lymphoid cell chimaeras made with nude athymic lpr (lymphoproliferation) mouse recipients.

C57BL/6 mice (B6) which are homozygous at the nu (nude, athymic) and lpr (lymphoproliferation) locus (B6 nulpr) are short-lived. We showed previously that increased survival could be obtained by grafting lymphoid cells from euthymic lpr-homozygous B6 mice (B6 lpr) mice ([lpr----nulpr] chimaeras), but curiously enough not from normal (B6 wild) mice ([wild----nulpr] chimaeras). Moreover female, but not male, [lpr----nulpr] chimaeras developed spleen and lymph node enlargement. In the present paper the distribution and absolute concentrations of all serum immunoglobulin (Ig) isotypes have been determined in these chimaeras and their controls. All chimaeras displayed whole serum Ig levels higher than those of B6 wild mice, suggesting a successful reconstitution of the athymic recipients by the grafted lymphoid cells, but two types of chimaeras were peculiar. The short-lived [wild----nulpr] chimaeras showed a proportion of IgM as high as ungrafted B6 nulpr mice, suggesting a deficient down-regulation of IgM production by the grafted B6 wild-type lymphoid cells. The [lpr----nulpr] female chimaeras recovered a long lasting overexpression of all Ig isotypes, like B6 lpr mice, while all the other chimaeras showed a transient overexpression only. Since neither lymphadenopathy nor persistent increase of serum Ig levels were observed in [lpr----nu] chimaeras, our data confirmed the need for a genetically lpr host to allow the significant development of the lpr syndrome.

Animals↗

PubMed1992

Comparison of the N- and O-linked glycopeptides of lymph node cells from C57 BL/6 lpr/lpr and C57 BL/6 mice.

We have tested the hypothesis that some phenotypic characteristics of the lymphocytes from mice with lymphoproliferative disease (lpr) could be explained by abnormal glycosylation of membrane proteins. Lymph node cells from normal C57 BL/6 and from C57 BL/lpr mice were labelled with tritiated sugars. Membrane proteins were released with trypsin, then with pronase. After complete pronase digestion, glycopeptides were first separated on Bio Gel P-6 and then on Con A-Sepharose. Fractions not binding to Con A (Con A negative) were also separated on Lens culinaris agglutinin-Sepharose. Marked differences between normal and lpr cells were noticed. First, there were more glucosamine-labelled peptides with very high molecular weight (eluting fast on Bio Gel P-6) on lpr cells than on normal lymphocytes. Second, the proportion of mannose-labelled peptides binding to Con A was smaller in the lpr cells. Third, among the Con A negative peptides, the proportion binding to Lens culinaris agglutinin was higher in lpr cells. Thus, lpr cells seem to carry more alpha 1-6 fucosylated chains and larger size carbohydrates. These alterations were also confirmed by gel electrophoresis of lectin-selected iodinated cell surface antigens and seem to be restricted to a very limited number of peptides. Thus, there may be primary changes in glycosylation in lpr cells. Alternatively, the glycosylation pattern of lpr cells may be characteristic for a subpopulation of T-lymphocytes that is expanded in this disease, or for a certain stage of activation. A large proportion of Con A-negative, Lens culinaris-positive peptides is a rather unusual feature in murine cells and requires further investigation.

Animals↗

PubMed1991

Adoptive transfer of viable motheaten pathology in sublethally irradiated beige recipient mice.

B6 viable motheaten (mev) mice are short-living autoimmune and immunodeficient mice. Most of the mev pathology is transferable into the B6 beige (bg) irradiated mouse by injection of mev haematopoietic cells. Indeed there is a rapid establishment of lung damage, thymus aplasia, inflammation and necrosis of peripheral joints, an increase of serological IgM concentrations and autoantibody levels as well as a rapid death. This mev-type pathology can be again obtained by transferring haematopoietic cells of these [mev----bg] chimeras into other irradiated bg mice, although the appearance of these serological and phenotypical symptoms seems to be more and more delayed when doing cascade transfers.

Animals↗

PubMed1989

Lymphoid cell transfers between adult C57BL/6 mice differing at the lpr and/or nu locus. Humoral immunity phenotype of the chimeras.

Congenic C57BL/6 mice (B6) homozygous only at the nu (nude, athymic) locus (B6 nu) or also at the lpr (lympho-proliferation) locus (B6 nu, lpr) were used as recipients for the transfer of spleen and/or lymph node cells from either normal B6 mice (B6+) or lpr-homozygous B6 mice (B6 lpr). Highly increased survival was obtained for [B6 lpr----B6 nu, lpr] chimeras, but not for [B6+----B6 nu, lpr] and [B6 nu----B6 nu, lpr] chimeras. All long-term survivors that were killed showed an increased responsiveness to the T-cell mitogen concanavalin A (Con A) but no change of responsiveness to the B-cell mitogen lipopolysaccharide (LPS). Some enlargement of spleen and lymph nodes was observed only in some specific [B6----B6 nu, lpr] chimeras (female recipients of spleen cells). Within a few weeks after cell grafting, all but [B6 nu----B6 nu, lpr] chimeras developed highly increased levels of serum immunoglobulins, as well as a higher occurrence of anti-single-stranded (ss) DNA containing sera. These chimeras had been constructed in order to dissect the components of the lpr phenotype etiopathology (primordial involvement of B and/or T lineage cells, lymphoid and/or environmental influences). Though the evolution of serological parameters showed some chimera type-specific features, it seems difficult to reconstitute the entire expression of the lpr phenotype.

Animals↗

PubMed1988

Radiation therapy of spontaneous autoimmunity: a review of mouse models.

The classical types of generalized autoimmune disease in man are systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Several murine strains which develop SLE and sometimes RA-like diseases are now available. They should help in the understanding of the etiopathology of SLE and RA. Basically two main therapeutic strategies which use solely irradiation have been tried; one being sublethal whole-body irradiation (WBI) and the other fractionated total lymphoid irradiation (TLI). Other protocols which combine lethal WBI and stem cell transplantation have often been attempted. It was regularly found that the bone marrow transplant (BMT) dictates the immune status of the recipient. This paper reviews the data published about NZB, NZB/W, BXSB and MRL mice in this context.

Animals↗

PubMed1988

Protein kinase C activators of the teleocidin family decrease the IgE-binding capacity of rat basophilic leukemia cells.

The tumor promoters 12-O-tetradecanoylphorbol-13-acetate (TPA) and the teleocidins (TCDs) had similar inhibitory effects on IgE binding onto the membrane of rat basophilic leukemia (RBL)-2H3 cells. The level of expression of the functional IgE Fc receptor (Fc epsilon R), as measured by CELISA, was decreased up to a maximum of 60% within 5 min-1 h of treatment. This inhibition was obtained at concentrations of 0.1 microgram/ml for most TCDs, of 1 microgram/ml for TPA and of 20 micrograms/ml for one TCD (olivoretin A). These molecules also decreased the amount of cell-bound IgE detectable by CELISA on cells that had been coated with IgE prior to TCD treatment. When incubated with RBL-2H3 cells for 30 min-2 h, the TCDs and TPA stimulated serotonin release. Depending on their concentration, they had various effects on IgE-plus antigen-induced serotonin release. It is suggested that the down-regulation of IgE receptor expression by these tumor promoters is mediated through protein kinase C activation and phosphorylation of the Fc epsilon R.

Animals↗

PubMed1988

Lymphoid cell transfers between adult C57BL/6 mice differing at the LPR locus. Lack of lymphadenopathy transfer and effects on host survival.

"1 pr" is an autosomal recessive locus which determines the lymphoproliferation of an abnormal T cell subset ("T lpr" cell subset). Though a thymus is necessary for the initiation of the lymphadenopathy, adult thymectomy does not interfere with the development of disease. C57BL/6 (B6) mice (either treated with cyclophosphamide or not), lpr heterozygous at the lpr locus, or not), and nu homozygous B6 mice (either homozygous at the lpr locus, or not) are refractory to the growth and massive proliferation of grafted cells of the aberrant T lpr cell subset, which polyclonally expands in lpr homozygous B6 mice. Their lack of expansion in B6 nu, lpr mice is surprising, since such animals may develop the lymphadenopathy under certain circumstances (thymus grafting). While the injection of normal B6 lymphoid cells does not improve the health of the B6 nu, lpr mice, but may even accelerate their wasting, the injection of B6 lpr lymphoid cells into B6 nu, lpr mice causes, after a transient wasting, a remarkable prolongation of survival. B6 nu recipients of B6 lpr lymphoid cells show no sign of wasting and survive like recipients of normal B6 (B6+) cells. Thus the "lpr type" lymphoproliferative potential is neither simply carried by the T lpr subset cells themselves, nor simply determined by the lpr environment of athymic, lpr homozygous mice, and it is also not readily reconstituted by grafting T lpr cells in athymic lpr mice.

Animals↗

PubMed1988

Partial expression of the lpr locus in the heterozygous state: presence of autoantibodies.

B6 mice heterozygous at the lpr locus (B6 +/lpr and B6 lpr/+) were compared with lpr homozygous mice (B6 lpr/lpr) and control mice (B6 +/+) for levels of serum immunoglobulin (Ig), presence of autoantibodies and rate of B-cell membrane immunoglobulin (mIg) capping. The total serum Ig levels in B6 +/lpr and B6 lpr/+ mice remained much below the high titres found in B6 lpr/lpr mice, and were close to the titres found in B6 +/+ mice. However, the presence of anti-single-stranded (ss) DNA antibodies and of anti-nuclear antibodies (ANA) was detected in most B6 +/lpr and B6 lpr/+ mice, although less frequently and in lower titres than in B6 lpr/lpr mice. The rate of mIg capping was higher in B6 +/lpr and B6 lpr/+ mice than in B6 +/+ mice, but the acceleration of the capping process remained inferior to the one found in B6 lpr/lpr mice. Therefore, the lpr locus is not totally recessive: some B-cell hyperactivity is expressed in the heterozygous state. This is in contrast with its lack of expression at the level of lympho-proliferation of the lpr-characteristic T-cell subset: none of the lpr heterozygous B6 mice displayed detectable lymphadenopathy.

Aging↗

PubMed1986

The C57B1/6 nu/nu, lpr/lpr mouse. III. Autoimmunity status.

C57B1/6 mice homozygous at the lpr (lymphoproliferation) locus display evident lymphadenopathy (in our B6 colony, primordially cervical lymph node enlargement) and autoimmunity (various autoantibodies). Four groups of mice corresponding to the diverse combinations of the lpr gene and the nu (nude, athymic) gene on the B6 genetic background have been compared for signs of lymphadenopathy. It occurred in all tested B6 +/+, lpr/lpr mice and none of the other groups (B6 nu/nu, +/+; B6 nu/nu, lpr/lpr and B6 +/+, +/+). B cell hyperactivity/autoimmunity was also evaluated by serum antibody analyses: higher serum immunoglobulin levels, anti-nuclear antibodies, anti-native DNA, anti-single stranded DNA, rheumatoid-like factors (anti-rabbit IgG), and natural antibodies against dinitrophenol and trinitrophenol haptens and their non cross reactive carriers: bovine serum albumin, hen egg albumin and keyhole limpet haemocyanin. Interestingly the levels of serum immunoglobulins and of some specific antibodies were somewhat higher in B6 nu/nu, lpr/lpr than in 'normal' B6 nu/nu, +/+, though they remained much lower than in B6 +/+, lpr/lpr animals. This suggests that the lpr gene may express its influence on the level of B cell activity in the absence of T lineage cells that would have normally matured in a thymus and that this effect of the lpr gene does not require the massive proliferation of T lineage cells observed in B6 +/+, lpr/lpr mice.

Aging↗