PubMed Health⌕ Search

Biomedical subjects

E A Olson

Publications and source records attributed to E A Olson.

7 recordsLinked to original sources
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↗
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

Marketing specialty physician services.

Physicians take into account many factors when making referral decisions, primarily provider expertise, good communication and good patient care. This professional paper will show that provider expertise and patient care are the most important factors in referral decisions, and that physicians rely primarily on direct experience for the information necessary to make a referral choice.

Advertising↗