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Biomedical subjects

B J Dalton

Publications and source records attributed to B J Dalton.

7 recordsLinked to original sources

Activation of the IL-1 gene in UV-irradiated mouse skin: association with inflammatory sequelae and pharmacologic intervention.

The relationship between ultraviolet irradiation, interleukin-1 production, and inflammatory sequelae and the pharmacologic inhibition of these events was investigated in Balb/c mice exposed to ultraviolet irradiation from a bank of six Westinghouse FS40 sunlamps. The resulting edema (66% increase), inflammatory cell infiltration, and rise in the acute-phase reactant (fourfold) serum amyloid P component was preceded by the activation of the interleukin-1 beta gene and enhanced product formation. Administration of dexamethasone, which is known to inhibit interleukin-1 production, inhibited the inflammatory response to ultraviolet irradiation. Thus, production of interleukin-1 may be one of the initial events leading to the consequences of ultraviolet irradiation exposure.

Animals

Interleukin-1 release by rat synovial cells is dependent on sequential treatment with gamma-interferon and lipopolysaccharide.

To determine the potential regulatory mechanisms involved in synovial cell interleukin-1 (IL-1) release, the ability of gamma-interferon (gamma-IFN) to influence IL-1 release was assessed. Rat synovial cells cultured in the presence of a variety of stimuli, including lipopolysaccharide (LPS), failed to release IL-1. However, pretreatment of synovial cells with gamma-IFN, followed by LPS stimulation, resulted in increased levels of intracellular IL-1 as well as release of IL-1 from the cell. The level of IL-1 release was dependent on the concentration of both gamma-IFN and LPS, and on length of exposure to the gamma-IFN. The kinetic and dose requirements for gamma-IFN-dependent IL-1 release were similar to those for Ia antigen expression, but LPS was necessary for IL-1 messenger RNA induction, intracellular IL-1 accumulation, and IL-1 release. In addition, sequential treatment, i.e., gamma-IFN followed by LPS, was essential for IL-1 induction. Substitution of phorbol ester or calcium ionophore for gamma-IFN did not result in similar IL-1 release. In addition, induction of IL-1 messenger RNA by another stimulus was not sufficient to result in IL-1 release following LPS treatment. These results suggest that release of IL-1 by rat synovial cells requires the production of a regulatory signal, which is inducible by gamma-IFN.

Animals

Antigenic properties of human lymphoblastoid interferons.

Most virus-induced human lymphoblastoid interferons examined contained variable proportions of the Le and F antigenic species described for human leukocyte interferon. The F species was not detectable in interferons liberated spontaneously from human lymphoblastoid cells in culture. Lymphoblastoid interferons differed considerably in their interaction with the same anti-interferon serum. Spontaneous interferons required approximately ten times less antibody for neutralization than interferon induced by virus in the same cultures or in Namalva cells. The findings suggest that either spontaneous interferons contain fewer inactive antibody-binding molecules than virus-induced lymphoblastoid interferons or the number and distribution of antibody-combining sites, and possibly other surface properties of the interferon molecule, may be influenced by the manner in which spontaneous and induced interferons egress from the cells.

Antigens

Antigenic properties and heterospecific antiviral activities of human leukocyte interferon species.

Human interferon obtained in peripheral leukocytes was purified approximately 1000-fold by affinity chromatography on anti-leukocyte interferon globulins coupled to Sepharose 4B, and by filtration on SDS-Sephadex G-100. The interferon was subsequently resolved into two molecular species by adsorption chromatography on SDS-hydroxylapatite. The two species which were eluted at different phosphate molarities from hydroxylapatite, could also be distinguished on the basis of electric charge properties and they migrated at different rates in SDS-polyacrylamide gels. Crossneutralization tests with monospecific rabbit anti-leukocyte and anti-fibroblast interferon sera revealed that the two species possessed leukocyte interferon-specific antigenic determinants. Both were immunogenic in mice and they were neutralized to a comparable degree by antisera against either component. A variable degree of antiviral activity was expressed by both interferon components in bovine, porcine and murine cells. However, the two interferon species were equally active in this respect, and the protective effects exhibited in homologous and heterologous cell cultures were similarly susceptible to reduction by beta-mercapto-ethanol. We conclude that the two molecular species of human leukocyte interferon are biologically similar.

Animals

Production of antibodies to human interferons in mice.

Neutralizing antibodies were raised in mice that had been inoculated repeatedly with moderate quantities of human leukocyte interferon highly purified by affinity chromatography on immobilized anti-interferon globulins. Interferon preparations of lesser purity sensitized the mice to subsequent inoculations of interferon and almost invariably caused death before anti-interferon titers developed. Antibody-purified interferon stabilized by sodium dodecyl sulfate was a superior antigen to interferon that had received mouse serum albumin as an additive. The amount of antibody could be augmented by experimental induction of ascites. The antibodies specifically neutralized leukocyte and lymphoblastoid interferons but not those interferons obtained cultures of human foreskin fibroblasts, embryonic kidney cells, and amnion cells.

Animals

Biological properties of human leukocyte interferon components.

Human leukocyte interferon, purified approximately 1000-fold by affinity chromatography on immobilized anti-interferon globulins and SDS-Sephadex filtration, was resolved into one major and one minor component by adsorption chromatography on hydroxylapatite and electrophoresis in polyacrylamide gels. These components were indistinguishable in their capacity to protect bovine, porcine and murine cells, and the antiviral activities of both were equally susceptible to reduction by beta-mercaptoethanol. They were neutralized to the same degree of rabbit anti-leukocyte interferon but were not neutralized by rabbit antifibroblast interferon serum. Mice immunized with either component developed antibodies to both but failed to form antibodies against human fibroblast interferon. Our present evidence indicates that the two components posses at most only minor structural and antigenic dissimilarities.

Animals

Multiple active sites on human interferons.

Human interferons stimulated in peripheral leukocytes and foreskin fibroblasts are active in cultures of human and rabbit cells. The dominant factors in leukocyte and fibroblast interferons responsible for antiviral activity in rabbit cells were shown to be antigenically distinct from each other as well as from rabbit interferon. In addition, leukocyte interferon contained also a minor component with antigenic determinants characteristic of fibroblast specificity, which could be isolated by affinity chromatography on Sepharose-bound antibodies directed against firboblast interferon. Neutralization tests with selected anti-interferon sera suggested that the antiviral activities of leukocyte and fibroblast interferons in human and rabbit cells were associated with single molecules. A model is proposed where molecules of human interferon contain multiple reactive sites each of which is capable of interaction with cells of a different species. The number and distribution of these determinant sites may vary with the source of the human interferon and account for the differential in antiviral protection expressed in homologous and phylogenetically unrelated host cells.

Animals