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Biomedical subjects

L L Kosuda

Publications and source records attributed to L L Kosuda.

6 recordsLinked to original sources
PubMed1992

The in vitro effects of mercury on peritoneal leukocytes (PMN and macrophages) from inbred brown Norway and Lewis rats.

The present paper demonstrates that HgCl2 can affect rat peritoneal polymorphonuclear leukocyte (PMN) and macrophage (M phi) functions in vitro. In addition, we have noticed that these effects of mercury vary according to the rat strain: for example, HgCl2 stimulates H2O2 release from Lewis (LEW) but not Brown Norway (BN) PMN. Similarly, LEW M phi produce high levels of H2O2 when exposed to HgCl2 in vitro, whereas BN M phi do not. Finally, mercury inhibits erythrophagocytosis of both LEW and BN "resident" peritoneal M phi. Preliminary experiments using M phi from other rat strains have also shown that MAXX M phi are stimulated by HgCl2 to release H2O2 in vitro, whereas Yoshida M phi are inhibited. Differences in lymphocyte responses (e.g. delayed-type hypersensitivity reactions and mitogen stimulation) between rats of various strains are well known. To these examples one may now add variations in PMN and M phi responses to mercury and possibly other metals. Our results suggest that caution should be exercised in interpreting the outcome of immunotoxicity studies in experimental animals. In particular, outbred rats may not provide appropriate models, that might be better obtained by comparative investigations of rats from various inbred strains.

Animals↗
PubMed1991

Reduction of the RT6.2+ subset of T lymphocytes in brown Norway rats with mercury-induced renal autoimmunity.

Chemically induced autoimmunity is a recently recognized environmental hazard that may affect individuals genetically predisposed to autoimmune disease and chronically exposed to certain chemicals. For example, moderate concentrations of mercury may lead to renal autoimmune disease in a small but significant percentage of the exposed population. Mercury also induces autoimmune glomerulonephritis in susceptible Brown Norway (BN) and MAXX inbred strain rats. Autoimmune responses, directed to epitopes of the renal glomerular basement membrane (GBM), are rapid in onset and have a self-limiting course in mercury-treated rats. Both regulatory T cells and idiotype-anti-idiotype network have been implicated in the resolution of this autoimmune process. In our investigations of immune regulation of mercury-induced autoimmune glomerulonephritis, we have used flow cytometry to quantitate lymphocyte subpopulations in the spleen and lymph nodes of mercury-treated and control BN rats. Of particular interest was the RT6+ T cell subset, that appears to have important immunoregulatory properties in a rat model of autoimmune insulin-dependent diabetes mellitus. Spleen and lymph nodes from control BN rats contained 22 and 52%, respectively, RT6+ cells. Spleens from mercury-treated animals contained 21% RT6+ cells on Day 10 of treatment, 13% on Day 17, 16% on Day 24 and 20% on Day 30. Lymph nodes from the same rats had 36% RT6+ cells on Day 10, 23% on Day 17, 29% on Day 24, and 28% on Day 30. The decrease in RT6+ cells correlated inversely with autoimmune responses to GBM, which peaked on Days 17-24 and declined by Day 30. Moreover, autoimmune responses were also associated with elevated RT6-:RT6+ T cell ratios. Similar results were obtained in two additional groups of BN rats, comprising both younger and older animals, sacrificed at Day 18 of mercury treatment. Analysis of other lymphocyte subpopulations demonstrated a decrease of CD4+ and CD5+ cells, whereas B cells as well as CD8+, IL-2 receptor+, and MHC class II+ subsets showed no consistent correlation with the onset or resolution of the autoimmune process. These findings suggest that mercury-induced changes in RT6+ T lymphocytes may be related to the development of renal autoimmune disease in genetically predisposed BN rats.

ADP Ribose Transferases↗
PubMed1978

Autoantibodies to acrosomal antigens of spermatozoa in vasectomized mice.

A total of 102 mice from seven different inbred strains were vasectomized or sham vasectomized. Sera from these animals were collected before vasectomy and at 7 and 10 months after the operation. Indirect immunofluorescence on sperm smears showed that 26 per cent of vasectomized mice had antibodies to arosomal antigens of spermatozoa. This response was restricted to three of seven strains. None of the sera obtained from animals before vasectomy or from sham-vasectomized control mice contained similar antibodies.

Acrosome↗
PubMed1977

Sperm autoantibodies in vasectomized rats of different inbred strains.

An immune response to antigens of spermatozoa occurs after vasectomy in rats of some inbred strains, but not in others. Antibodies to rat spermatozoa were detected by indirect immunofluorescence in some of the serums of vasectomized rats of the following strains: 80 percent of Lewis, 47 percent of Brown Norway, 13 percent of Buffalo, 12 percent of Wistar-Furth, and 11 percent of ACI rats. No such antibodies were detected in the serums of vasectomized Fischer, Dark Agouti, and Sprague-Dawley rats.

Acrosome↗
PubMed1976

Immune complex orchitis in vasectomized rabbits.

The results of the present study show that bilaterally vasectomized rabbits with high levels of antibodies to sperm antigens frequently develop an orchitis associated with granular deposits of rabbit IgG and C3 in the basement membranes of seminiferous tubules. The immune deposits correspond in location to electron-opaque deposits seen by electron microscopy. The "membranous orchitis" is characterized by thickening of tubular basement membranes, acc-mulation of macrophages and a few polymorphonuclear leukocytes, and destruction of the basal lamina, of the Sertoli and spermatogenetic cells. The pathogenetic role of the immune deposits and the possibility that they contain antigen-antibody complexes is indicated by: (a) selective accumulation of IgG and C3 granular deposits along the basement membranes of seminiferous tubules in rabbits producing high and persistent levels of antibodies to sperm antigens; (b) the elution of immunoglobulins from tissues with chaotropic ion-containing buffers, acid buffers, or heat; (c) the observation that the immuno-globulins accumulated in the testis contain antibody to sperm antigens; and (d) the demonstration of sperm antigens in a location similar to that of IgG and C3. It is postulated that sperm antigen-antibody complexes are formed in the basement membranes of seminiferous tubules when antigens leaking out of the tubules react with specific antibody coming from the circulation. In two rabbits with higher levels of circulating antisperm antibodies and severe orchitis, granular deposits of IgG and C3 were also present in renal glomeruli. Immunoglobulins eluted from the kidneys contained antibody with antisperm activity. These findings are consistent with the hypothesis that in some vasectomized rabbits extratesticular lesions may develop by a mechanism comparable to that of chronic serum sickness.

Animals↗