Biomedical subjects

M A Lynes

Publications and source records attributed to M A Lynes.

At least 19 recordsLinked to original sources

PubMed2002

Metallothionein suppresses collagen-induced arthritis via induction of TGF-beta and down-regulation of proinflammatory mediators.

Metallothionein is a low molecular weight, cysteine-rich, stress response protein that can act as an antioxidant and as an immunosuppressive agent in instances of antigen-dependent adaptive immunity. In this context, we assessed the therapeutic potential and mechanisms of action of metallothionein in a collagen-induced arthritis model. Repeated administration of metallothionein-I + II during the course of disease dramatically reduced the incidence and severity of the disease. Joint tissues isolated from boostered paws of metallothionein-I + II-treated mice expressed significantly reduced levels of proinflammatory mediators, such as tumour necrosis factor (TNF)-alpha and cyclooxygenase-2, when compared with those of control-treated mice. Lymph node cells obtained from metallothionein-I + II -injected mice exhibited a significant decrease in the proliferative response and a remarkable increase in tumour growth factor (TGF)-beta production in response to type II collagen. Taken together, these results suggest that metallothionein-I + II promote the development of type II collagen-specific, TGF-beta-producing cells to antagonize the expansion of arthritogenic cells. This could lead to local suppression of inflammatory responses by inhibiting the expression of proinflammatory molecules. Thus, this study demonstrates the suppressive effects of metallothionein on collagen-induced arthritis, and indicates that there may be a potential therapeutic application for manipulation of metallothionein during the treatment of autoimmune disorders.

Animals↗

PubMed2001

Effects of hemizygous CD45 expression in the autoimmune Fasl(gld/gld) syndrome.

Mice homozygous for the Fasl(gld/gld) mutation cannot initiate apoptosis via the Fas/Fasl pathway and develop an autoimmune disease characterized by the accumulation of CD4(-)/CD8(-) (DN) T cells and a progressive T cell anergy. These DN T cells express a high-molecular-weight isoform of the membrane PTPase CD45 (B220). We have produced a Fasl(gld/gld) mouse strain with only one functional CD45 allele (CD45(+/-), Fasl(gld/gld)) in order to explore the role that CD45 plays in the lymphoaccumulation and proliferative capacity of the DN T cells. In contrast to CD45(+/+), Fasl(gld/gld) mice, CD45(+/-), Fasl(gld/gld) mice display a 10-fold reduction in the DN T cell population and have decreased levels of anti-DNA antibodies and total serum Ig. However, enriched DN T cell populations remain unresponsive to mitogenic stimulation, but do display altered patterns of tyrosine phosphorylation. These data indicate that CD45 is essential to the accumulation of DN T cells in Fasl(gld/gld) mice and implicate CD45 as a component of the process of deletion that normally governs the composition of the T cell population.

Animals↗

PubMed2001

In vivo manipulation of endogenous metallothionein with a monoclonal antibody enhances a T-dependent humoral immune response.

Metallothionein (MT) is a small stress response protein that can be induced by exposure to heavy metal cations, oxidative stressors, and acute phase cytokines that mediate inflammation. In previous experiments, we have shown that exogenous MT can affect cell proliferation, macrophage and cytotoxic T lymphocyte function, and humoral immunity to T-dependent antigens. In the studies described here, we have explored the effect of a monoclonal anti-MT antibody (clone UC1MT) on the role that endogenous MT plays in the humoral immune response. In vivo injection of UC1MT significantly increased the humoral response to simultaneous challenge with ovalbumin (OVA). In contrast, mice immunized with OVA in the presence of an isotype-matched antibody control (MOPC 21) showed no change in the anti-OVA humoral response. The predominant anti-OVA response that was enhanced by UC1MT treatment was the IgG(1) response; the IgG(2a) anti-OVA response was not altered by UC1MT treatment. UC1MT treatment increased the numbers of IgG anti-OVA secreting cells as measured by ELISPOT assay, suggesting that blocking the effects of MT synthesized during the immune response augments the differentiation of antigen-specific plasma cells. The percentages of T and B cells in the spleens of animals from each treatment group were not significantly different, suggesting that this regimen of UC1MT treatment does not significantly affect hematopoiesis, but rather alters antigen-induced differentiation of lymphocytes. These observations are compatible with previous results from our laboratory that suggest that endogenous MT synthesized during the normal immune response or as a consequence of toxicant exposure suppresses in vivo immune function. In light of the fact that significant amounts of MT can be synthesized during toxicant exposure, manipulation of MT levels with an anti-MT antibody may ultimately represent an important therapeutic approach to the treatment of immune dysfunctions that result from toxicant exposure.

Animals↗

PubMed2001

Automated real-time measurement of chemotactic cell motility.

We have developed a novel method, (ECIS/taxis), for monitoring cell movement in response to chemotactic and chemokinetic factors. In this system, cells migrate in an under-agarose environment, and their positions are monitored using the electric cell-substrate impedance sensor technology to measure the impedance change at a target electrode, that is lithographed onto the substrate, as the cells arrive at the target. In the studies reported here, Dictyostelium discoideum was used as a prototypical, motile eukaryotic cell. Using the ECIS/taxis system, the arrival of cells at the target electrode was proportional to the dose offolate used to stimulate the cells and could be assessed by changes in resistance at the electrode. ECIS/taxis was readily able to distinguish between wild-type cells and a mutant that is deficient in its chemotactic response. Finally, we have shown that an agent that interferes with chemotactic motility leads to the delayed arrival of cells at the target electrode. The multi-well assay configuration allows for simultaneous automated screening of many samples for chemotactic or anti-chemotactic activity. This assay system is compatible with measurements of mammalian cell movement and should be valuable in the assessment of both agonists and antagonists of cell movement.

Animals↗

PubMed2000

Augmented humoral immune function in metallothionein-null mice.

Stress response proteins can play integral roles as modulators of cellular function and can be involved in mechanisms that are important to immune function. Metallothionein (MT), a cysteine-rich stress response protein, has been shown to play numerous roles in the cell: it serves as a reservoir of essential heavy metals, it scavenges free radicals, and it can sequester heavy metals. These various functions suggest that MT may also participate in modulating immune responses. In previous work, we have shown that exogenous metallothionein can suppress the developing humoral immune response when coinjected with antigen. The present study was designed to evaluate the effects of endogenous MT on the development of humoral immunity. We compared the humoral immune function of animals with a targeted disruption of Mt-1 and -2 genes (MTKO) and their wild-type counterparts. MTKO mice displayed a significantly higher humoral response to challenge with ovalbumin (OVA) compared to wild-type controls. The secondary anti-OVA response in MTKO mice is as much as 58% higher than the response in control mice injected at the same time. Overall circulatory immunoglobulin levels are also substantially higher in MTKO mice (0.039 mg/ml IgM and 0.42 mg/ml IgG) than wild-type controls. MTKO mice displayed increased B cell differentiation following OVA challenge and an enhanced lymphoproliferative response to mitogenic stimulation. These changes in immune functional capacity occur in the context of changes in the makeup of the lymphoid compartments of the blood and spleen. There are substantially fewer T and B cells in the circulation of MTKO mice, but more T cells in the spleen of these mice than in control animals. Finally, we have found that splenocytes from MTKO animals displayed significantly elevated levels of NF-kappaB activity compared to wild-type controls. In conclusion, we have provided evidence that endogenous metallothionein can modulate the immune response in vivo and that intracellular MT may modulate immune function by regulation of transcription factor activity.

Animals↗

PubMed1999

Variables controlling the expression level of exogenous genes in Dictyostelium.

Ectopic expression of genes from recombinant plasmids is commonly used to study gene function. In Dictyostelium, three drug resistance cassettes are commonly used as selectable markers in vectors. We report here a comparative study of the expression of green fluorescent protein (GFP) gene from vectors containing each of the drug-resistant cassettes. The expression was highest in cells transformed with the vectors containing the neomycin-resistant cassette (pDNeoGFP), followed by the hygromycin-resistant cassette (pDHygGFP) and the blasticidin-resistant cassette (pDBsrGFP). The level of GFP expression was directly related to the copy number of the vector in transformants. In turn, the copy number of the vector depended on the drug resistance cassette as well as the concentration of the drug used in selection. In general, cells with higher copy numbers could be selected by a higher drug concentration. The expression of GFP was also affected by the method of transformation. For pDHygGFP, expression of GFP was much higher in cells transformed by electroporation than those transformed by calcium phosphate coprecipitation. However, only a slight difference was observed for pDNeoGFP or pDBsrGFP.

Animals↗

PubMed1999

Metallothionein-induced suppression of cytotoxic T lymphocyte function: an important immunoregulatory control.

Exposure to environmental toxicants can alter a variety of cellular functions that are critical to immune function. Cellular responses to these changes include increased synthesis of a number of stress proteins, some of which have been shown to have immunomodulatory capacity. One of these stress proteins, metallothionein (MT) is a low molecular weight, cysteine-rich protein that can be induced by exposure to environmental stressors as well as many inflammatory and tumorigenic agents. As a consequence, high levels of MT have been found at sites of inflammation and in certain types of neoplastic cells. In light of the suppressive effects that MT has been found to have on T-dependent humoral immunity, we investigated the potential role that MT might play in cell-mediated immune functions that could contribute to antitumor immunity. We found that MT can cause dramatic decreases in murine cytotoxic T lymphocyte (CTL) activity against allogeneic target cells. MT also reduces the proliferative response of CTLL-2 cells to cytokines, and decreases the level of major histocompatibility complex (MHC) Class I and CD8 molecules detectable on the surface of lymphocytes, while having no significant effect on the level of CD4. These findings suggest that the immunosuppressive effects of MT may at least in part reflect interference with cell-cell interactions that are ordinarily critical to cell-mediated immunity. Despite this suppressive effect on CTL functioning, MT was found to augment mixed lymphocyte reactions (MLRs) in concert with increased interleukin-2 receptor (IL-2R) expression. This MT-augmented proliferation was observed in both allogeneic and syngeneic MLR. Taken together, these results indicate that MT may increase the number of immature T cells, but decrease their differentiation to the effector CTL stage. These effects of extracellular MT on T-cell function may contribute to the immunosuppression of cell-mediated immunity that has been ascribed to inducers of MT synthesis. In addition, they may point to the manipulation of MT levels as a means of reducing the undesirable immunomodulatory effects of these agents.

Animals↗

PubMed1998

SHP-1 deficiency in B-lineage cells is associated with heightened lyn protein expression and increased lyn kinase activity.

SHP-1 protein tyrosine phosphatase is a critical regulator of signal transduction in hematopoietic cells. In the present study, we derived two pre-B cell lines, PBCL-1 and PBCL-2, from normal and SHP-1-deficient motheaten mice, respectively, and characterized hyperphosphorylated proteins in PBCL-2 cells to identify SHP-1-regulated molecules. Two proteins of 56 and 53 kDa (p56/p53) in PBCL-2 cells showed heightened phosphorylation (3- to 6-fold) in comparison with those in PBCL-1. p56/p53 were identified as the two forms of the lyn protein tyrosine kinase (p56/p53lyn), which showed increased kinase activity in PBCL-2 cells. Interestingly, the protein levels of p56/53lyn were found to be 3- to 6-fold higher in PBCL-2 cells than those in PBCL-1, whereas the transcript levels of lyn in the two cell lines were comparable. A modest increase in p56/53lyn protein expression was also detected in primary spleen B cells of motheaten mice. Thus SHP-1 deficiency in B-lineage cells, especially pre-B cells, is associated with increased lyn protein expression and kinase activity. These data indicate a role for SHP-1 in regulating lyn through a post-transcriptional mechanism.

Animals↗

PubMed1996

Interactions of metallothionein with murine lymphocytes: plasma membrane binding and proliferation.

Metallothionein (MT) is a thiol rich protein that has been well characterized for its ability to bind and sequester heavy metal cations, free radicals and other reactive toxicants. In addition to induction by these stressors, MT gene expression is upregulated by several cytokines of the acute phase response. In previous work, we have shown that MT can alter aspects of lymphocyte function. MT alone induces modest proliferation of unfractionated splenocytes and acts synergistically with T cell- and B cell-specific mitogens. In contrast, MT inhibits humoral responsiveness in vivo and reduces in vitro T cell responses to processed antigen. In this report, we describe the effects of MT on specific lymphocyte subpopulations in order to further characterize the mechanism of MT-mediated alterations of immune activity. MT binds to the plasma membrane of both T and B lymphocytes, but, in the absence of a costimulatory agent, MT induces lymphoproliferation only in B cells. MT also enhances the capacity of naive B lymphocytes to differentiate into plasma cells. These results demonstrate differential immunomodulatory activities of MT and may explain some of the diverse immunoregulatory effects associated with exposure to environmental toxins.

Animals↗

PubMed1996

Nonprotective effects of extracellular metallothionein.

Metallothionein (MT) is a small, cysteine-rich protein that is readily induced by exposure to heavy metal cations. In previous work, we have demonstrated that MT has several significant immunomodulatory properties. MT decreases antigen-specific humoral responses in vivo and inhibits the ability of T cells to proliferate in response to antigen presented in vitro. To further characterize the mechanism by which this protein inhibits responsiveness to antigen, we have examined the effects of MT on cell viability in an antigen-presentation assay. MT (20 microM) caused substantial death to both lymphocytes and monocytes after 3 days of culture. The observed toxicity cannot be attributed to either increased superoxide radical generation or to production of tumor necrosis factor by MT-treated macrophages. Fractionation of supernatants from MT-treated cells suggests that the agent responsible for causing cytotoxicity is a soluble factor of at least 30 kDa. These results counter the perception that metallothionein uniformly plays a protective role in metal-stressed individuals.

Analysis of Variance↗

PubMed1996

The phosphotyrosine phosphatase inhibitor-phenylarsine oxide restores defective phosphoinositide hydrolysis response in anergic C3H-gld/gld lymphocytes.

Mice homozygous for the gld (generalized lymphoproliferative disease) mutation develop both lymphadenopathy and autoimmune disease. CD4-CD8- (double negative, DN) T cells comprise the major population of T cells in mature C3H-gld/gld peripheral lymphoid tissues. These DN T cells are unresponsive to many forms of stimuli and have previously been shown to exhibit abnormally elevated levels of membrane phosphotyrosine phosphatase (PTPase) activity. In the present study, we demonstrate that IP3 production in response to mitogenic stimulation with Con A or anti-CD3 mAb (145-2CII) is significantly diminished in C3H-gld/gld lymphocytes when compared to that in congenic C3H(-)+/+ cells. The capacity to produce this second-messenger can be restored by pretreating C3H-gld/gld cells with the PTPase inhibitor, phenylarsine oxide (PAO). Although the inhibition of PTPase activity by treatment with PAO did restore C3H-gld/gld cell ability to produce IP3, the signal did not lead to lymphocyte proliferation, but instead to cell death. Our results suggest that the altered phosphoinositide hydrolysis observed in the mutant cells is related to their elevated membrane PTPase activity and that the anergy in these cells is at least in part related to the abnormally high activity of endogenous PTPases.

Animals↗

PubMed1996

Stress proteins as agents of immunological change: some lessons from metallothionein.

The stress response proteins each have somewhat unique characteristics that enable them to function under conditions of cellular stress, and to contribute to cellular survival in difficult times. The immune response is, by definition, a mechanism that often operates in times of cellular stress, and even creates stress during its operation. Cells called upon to respond to tissue damage caused by inflammation can have extraordinary demands placed upon them and surrounding tissue may suffer damaging conditions that were originally established to eliminate the source of the inflammation. Stress proteins may be released from some of these damaged cells as a programmed response to the stress, or as a simple consequence of excessive damage to the plasma membrane. In either instance, there is the opportunity for these stress proteins to interact with cells and proteins in the extracellular environment. It may be that those same characteristics that enable stress proteins to interact with structures within the cell also enable interactions outside the cell, but with dramatically different results. As has been found with MT, interference with these extracellular interactions may decrease the consequences of stress on the immune response, and may enable more effective immunity. It may also be possible to employ the various stress proteins to manipulate normal immune function.

Animals↗

PubMed1995

Immunomodulatory activities of extracellular metallothionein. II. Effects on macrophage functions.

Metallothionein (MT) is a thiol-rich protein that is rapidly induced by exposure to heavy metal cations. We have previously demonstrated that exogenous MT stimulates murine splenocytes to proliferate, but inhibits humoral responses to antigen. These observations suggest that metallothionein released from cells has a complex role in heavy metal-mediated immune dysfunction. Here we examine one possible mechanism by which MT mediates suppression of humoral immunity. Exposure of macrophages to 20 microM MT did not affect their ability to engulf opsonized sheep erythrocytes, but in the presence of 20 microM MT, peritoneal macrophages were stimulated to produce increased levels of oxygen radicals. These results correlated with observations that while macrophage phagocytosis of opsonized Candida albicans was unaltered by the presence of exogenous MT, killing of the engulfed yeast cells was dramatically enhanced by 20 microM MT. Amounts of free cadmium and zinc equimolar to that added as Zn,Cd-MT had no effect on candidacidal activity. MT was also found to significantly decrease lymphocyte proliferation mediated by macrophage activity. Biotinylated MT (MT-b) bound specifically to the plasma membranes of these macrophages, suggesting that membrane-associated molecules of the macrophage may transduce a signal mediated by MT binding. These results demonstrate that macrophages are a sensitive target for MT-mediated immunomodulation and that some of the consequences of the MT interaction with macrophages may be alterations in the capacity to produce an effective immune response and increased extracellular exposure to damaging free radicals.

Animals↗

PubMed1993

Immunomodulatory activities of extracellular metallothionein. I. Metallothionein effects on antibody production.

Extracellular metallothionein (Zn,Cd-MT) has previously been shown to be a potent inducer of lymphocyte proliferation and to synergize with polyclonal activators in proliferation assays. In this report, the effects of metallothionein on the development of humoral responsiveness are examined. In vivo, the specific anti-ovalbumin (OVA) IgG response was diminished by co-injection of Zn, Cd-MT, while total IgG levels remained unchanged. A similar reduction was also observed when Zn,Cd-MT was administered during the development of an anti-sheep red blood cell (sRBC) humoral response. When amounts of Zn and Cd equimolar to that associated with the Zn, Cd-MT were co-injected with OVA, humoral responsiveness was enhanced, in contrast to the suppression seen with Zn, Cd-MT. Apothionein lacking the available thiols associated with native Zn, Cd-MT had no effect on the development of humoral immunity. These results point to the thiols associated with the protein as the important determinants in the observed immunosuppression and this is supported by the capacity of UC1MT, a new monoclonal anti-MT antibody, to reverse MT mediated immunosuppression. No evidence was found to suggest that Zn,Cd-MT was interacting directly with OVA. Finally, in vitro experiments with LPS-stimulated splenocyte production of IgM correlated with the in vivo observations of Zn,Cd-MT. These data provide evidence for a significant role for MT in the development of metal-mediated immunomodulation and suggest that MT may also possess immunomodulatory functions under circumstances where MT is synthesized in the absence of heavy metal stress. Furthermore, it may be possible to take advantage of this system to exogenously manipulate the development of the immune response.

Adjuvants, Immunologic↗

PubMed1993

Dynamic associations of CD45 and Thy-1 on plasma membranes of C3H-gld/gld and C3H-lpr/lpr. I. Potential effects on proliferation and phosphatase activity.

Spatial associations of individual plasma membrane components have been proposed as being important in the functional coupling of these molecules. CD45 and Thy-1 associate on the membranes of both transformed and normal lymphocytes as measured by several different methods, and both of these molecules have been found to contribute to T cell activation and proliferation. Thy-1, however, lacks both transmembrane and cytoplasmic domains (it is linked to the plasma membrane through a glucosyl-phosphatidylinositol linkage), obliging the activation and proliferation signals that act through Thy-1 to be transduced by neighboring molecules. In the experiments reported here, the association of Thy-1 and CD45 was examined on lymphocytes from two mutant mouse strains, C3H-gld/gld and C3H-lpr/lpr, both of which exhibit lymphocyte activation and proliferation parameters significantly different from the control C3H/HeJ strain. No significant differences in Thy-1/CD45 association (measured by a heterologous epitope blocking assay) to distinguish mutant from wild-type thymocytes were found. However, spatial associations of CD45 and Thy-1 were altered on both mutant lymph node cells and splenic lymphocytes. These abnormal associations suggested possible effects on the membrane protein tyrosine phosphatase (PTPase) activity associated with CD45. Both C3H-gld/gld and C3H-lpr/lpr lymph node cells were found to have significantly elevated levels of membrane PTPase activity, and this elevation correlated with the anergy to mitogens that develops as these animals age. Finally, monoclonal anti-Thy-1 antibody (G7) reduced the PTPase activity of wild-type membrane isolates, suggesting that Thy-1/PTPase interactions may be a mechanism by which G7 provokes a lymphoproliferative response.

Animals↗

PubMed1992

Immunochemical Analysis of the Temporal and Tissue-Specific Expression of an Avena sativa Plasma Membrane Determinant.

An immunoglobulin Mk monoclonal (F8IVE9) antibody raised against oat (Avena sativa cv Garry) root homogenate has been produced and characterized. The predominant target bound by this antibody is a 62-kilodalton protein (p62) that is expressed in both oat root and oat shoot cells. Treatment of the oat antigen with periodate, or with recombinant N-glycanase, affects the F8IVE9 binding to the antigen, suggesting that the specific epitope for this monoclonal antibody involves a carbohydrate determinant. Levels of p62 present in cells of the oat root increase approximately twofold as the root tissue matures during the first 11 days postgermination. In contrast, levels of expression in shoot tissue remain relatively constant during the same period. The p62 antigen has been shown to be expressed at the plasma membrane by immunohistochemical means, by immunofluorescent labeling of protoplasts, and by enzyme-linked immunosorbent assay analysis of purified plasma membrane. The F8IVE9 antigenic target appears to be uniformly distributed through root tissue but is differentially expressed in specific sections of the shoot. F8IVE9 antibody also binds to antigens expressed in a number of other species, including clover, corn, pea, broccoli, mustard, and bean, and has been shown to bind to Samanea protoplast plasma membranes. This monoclonal antibody may prove to be useful for a variety of investigations, including an analysis of the specific patterns of cellular differentiation that occur during early morphogenesis, and the characterization of plasma membrane-associated elements in plants.

Journal Article↗

PubMed1991

Defects in gliding motility in mutants of Cytophaga johnsonae lacking a high-molecular-weight cell surface polysaccharide.

We previously observed (W. Godchaux, L. Gorski, and E.R. Leadbetter, J. Bacteriol. 172:1250-1255, 1990) that two mutants (strains 21 and NS-1) of the gliding bacterium Cytophaga johnsonae that were totally deficient in motility-dependent colony spreading, movement of rafts (groups) of cells as observed with a microscope, and movement of polystyrene-latex spheres that attached to the cell surface (observed in wet mounts) were also deficient in a high-molecular-weight cell surface polysaccharide (HMPS) and suggested a role for that substance in gliding motility. Antisera have been prepared against the purified HMPS, and these were used to select mutants specifically and highly deficient in the polysaccharide. All five such mutants had rates of colony spreading and raft movement that were much lower than those of the parent strain, but the rate of increase in colony diameter was higher than that found for strains NS-1 and 21 (which do not undergo raft movement at all). Unlike these latter two strains, the HMPS mutants retained the ability to move polystyrene-latex spheres over their surfaces. Hence, HMPS deficiency results in defective motility but not nonmotility, and the HMPS deficiency cannot fully explain the phenotype of mutants 21 and NS-1; in these strains, gliding must be affected by additional biochemical lesions. The HMPS may, nonetheless, be advantageous in that it supports greater gliding speeds.

Carbohydrates↗

PubMed1990

Extracellular metallothionein effects on lymphocyte activities.

Metal cation influences on the immune response have been reported in a wide variety of experimental systems. These influences can either result in the augmentation or suppression of immunological activities. In order to investigate possible mechanisms of these influences, we examined the role that a metal cation-induced protein, metallothionein (MT), might play. Our findings suggest that thioneins, either as apoproteins or when complexed as Cd,Zn-MT, Zn-MT, or Cd-MT, are capable of inducing lymphocyte proliferation. This level of induction is substantially reduced when Zn,Cd-MT is added to lymphocyte cultures in the presence of 50 microM 2-mercaptoethanol. Apoprotein, Zn,Cd-MT, Zn-MT and Cd-MT also augment LPS-induced proliferation of splenic lymphocytes. Only the Zn,Cd-MT preparation significantly augmented ConA-induced proliferation. Hg-MT and Cu-MT were inhibitory as additions in either LPS or ConA mitogen proliferation assays, and did not stimulate proliferation when added alone to lymphocyte cultures. The capacity to induce proliferation correlates with the measurable thiol level of the particular thionein. Interestingly, Zn,Cd-MT and apothionein had an equivalent number of accessible thiols. Although Zn, Pb, Hg and Cu lowered the number of these sites, the immunoreactivity of these MTs was not altered substantially except by Pb. These results suggest that some metal influences on lymphocytes might be through a thionein intermediary. Our results also demonstrate that thioneins complexed with certain metal cations are detrimental to the normal cellular activities of lymphocytes. At least in these circumstances, MT does not play a role as a protective agent.

Animals↗