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Biomedical subjects

H M Johnson

Publications and source records attributed to H M Johnson.

At least 163 records · Page 9Linked to original sources
PubMed1982

Cyclic GMP as the second messenger in helper cell requirement for gamma-interferon production.

Cyclic GMP and activators (acetylcholine, E. coli heat-stable toxin) of guanylate cyclase were capable of completely replacing the helper cell or interleukin 2 requirement for gamma-interferon (IFN gamma) production by Lyt-1-,2+ cells from C57BL/6 mouse spleen cells. The cyclic GMP help was independent of DNA synthesis or proliferation in the IFN gamma-producing cells, because cyclic GMP reversed mitomycin C blockage of IFN gamma production but did not reverse the inhibition of DNA synthesis. Thus, the findings presented here are unrelated to the question of the second messenger role of cyclic GMP in the activation of lymphocytes for DNA synthesis and cellular proliferation. The cyclic GMP help for IFN gamma production was antagonized by cyclic AMP and inducers (isoproterenol) of adenylate cyclase.

Animals↗
PubMed1982

Regulation of murine macrophage Ia antigen expression by an immune interferon-like lymphokine: inhibitory effect of endotoxin.

The initiation of antigen-specific, T-dependent immune responses by macrophages requires their expression of Ia antigens. Ia antigen-deficient (Ia-) peritoneal exudate or P388D1 cell line macrophages, when incubated for 2 to 3 days with partially purified immune interferon (IFN-gamma), expressed Ia antigen, as detected by antibody-and-complement-mediated cytotoxicity. This paper reports that bacterial endotoxin (lipopolysaccharide, LPS) inhibited both IFN-gamma induction of macrophage Ia antigen expression and IFN maintenance of the Ia+ state in a dose-dependent manner. In the absence of IFN-gamma, LPS had no significant effect on macrophage Ia antigen expression. The inhibitory effects of LPS were abrogated by the addition of indomethacin into the culture medium. Further, 10(-10) to 10(-6) M exogenous prostaglandin E2 or 10(-6) to 10(-4) M exogenous dibutryl 3'5' cyclic adenosine monophosphate also inhibited IFN-gamma regulation of macrophage Ia antigen expression. The data suggest that LPS inhibits IFN-gamma regulation of macrophage Ia antigen expression by stimulating macrophage prostaglandin E2 production, and consequently enhancing intracellular cAMP levels. The data outline an inhibitory pathway involved in the regulation of macrophage Ia antigen expression, and may explain, in part, reported immunosuppressive effects of LPS.

Animals↗
PubMed1981

Inverse relationship between immune interferon induction and mitogen effects on the maturation of the primary antibody response.

Staphylococcal enterotoxin A (SEA) is both a potent inducer of immune interferon (IFN-gamma) and suppressor of the murine primary in vitro plaque-forming cell (PFC) response to the thymus-dependent antigen sheep erythrocytes (SRBC). Staphylococcal enterotoxin D (SED), which is structurally related to but antigenically different from SEA, is, in contrast, a poor inducer of IFN-gamma but a potent accelerator of PFC response maturation. SED added to cultures from 0.01 to 1.0 microgram/ml induced profound enhancement of the PFC response on day 3 of culture. SEA caused no acceleration of PFC maturation and suppressed the day 5 PFC response over an equivalent dose range. At the same concentration, SED only poorly induced IFN-gamma, while SEA was a potent IFN-gamma inducer. SED induced DNA synthesis in C57Bl/6 spleen cell cultures but not athymic nude (Nu/Nu) spleen cells, suggesting that SED is a T-cell mitogen. SED was most effective in accelerating PFC maturation and increasing the magnitude of the PFC response when added to cultures at the time of SRBC addition. SED was an equally effective adjuvant for SRBC of both high and low immunogenicity. Thus, two mitogens that are structurally related have diametrically opposite effects on the primary in vitro thymus-dependent antibody response that maybe related to their relative abilities to induce IFN-gamma. These effects could be related to differential activation of T-cell subpopulations.

Animals↗
PubMed1981

Regulation of the production of immune interferon and cytotoxic T lymphocytes by interleukin 2.

The activation of alloantigen-specific cytotoxic T lymphocyte precursors is dependent upon the presence of both macrophages and helper T cells or regulatory molecules derived from these facilitative cells. Three biochemically distinct helper factors have been identified: interleukin 1 (macrophage-derived), Interleukin 2 (T cell derived), and immune interferon. All 3 factors are found in supernatants of mixed lymphocyte cultures (MLC), however, the removal of macrophages from these cultures completely ablates the production of these factors as well as the induction of cytotoxic T lymphocytes (CTL). The addition of IL 2 to these macrophage-depleted MLC restores the ability of responder T cells to: 1) bypass the requirement for macrophage soluble function, 2) produce immune interferon, and 3) generate CTL. The kinetics and dose response of immune interferon production in response to IL 2 correlates with the generation of CTL. The production of immune interferon as well as the generation of CTL requires T cells, alloantigen, and IL2. Furthermore, the induction of CTL by IL2 was neutralized by the addition of anti-immune interferon. These data suggest that: 1) the regulation of immune interferon production is based on a T to T cell interaction mediated by IL 2, and 2) immune interferon production may be required for IL 2 induction of CTL. These findings are consistent with the hypothesis that the induction of CTL involves a linear cell-factor interaction in which IL 1 (macrophage-derived) stimulates T cells to produce IL 2, which in turn stimulates other T cells to produce immune interferon and become cytotoxic.

Animals↗
PubMed1981

Antibody to staphylococcal enterotoxin A-induced human immune interferon (IFN gamma).

Antiserum to human gamma interferon (IFN gamma) was produced in rabbits immunized with partially purified (10(4.8) to 10(6.2) antiviral U/mg protein) staphylococcal enterotoxin A-induced IFN gamma. Staphylococcal enterotoxins, phytohemagglutinin M, concanavalin A, and pokeweed mitogen-induced antiviral activity in human leukocyte cultures was neutralized to undetectable levels by the antiserum. However, human leukocyte interferon (IFN alpha), human fibroblast interferon (IFN beta), and mouse interferons were not neutralized by the antiserum. After determining the antiserum was specific for IFN gamma and did not neutralize other known types of interferon, it was used with antibody to human IFN alpha to demonstrate the type(s) of interferon stimulated by some new inducers and antigens. Galactose oxidase- and calcium ionophore-induced interferons were neutralized to undetectable levels by the antiserum to IFN gamma. Interferon produced in leukocyte cultures from tuberculin-negative individuals stimulated with tuberculin-purified protein derivative or old tuberculin was IFN alpha, whereas interferon from tuberculin-positive individuals was a combination of alpha and gamma IFN. In addition, the antiserum neutralized the anticellular and natural killer cell enhancement activities of IFN gamma preparations. The specificity of this antiserum for IFN gamma indicates that it is an additional, powerful tool for identifying and classifying known and new interferons produced in vitro or in vivo and for investigating the role(s) of IFN gamma during the course of infectious, neoplastic, and autoimmune diseases.

Animals↗
PubMed1980

The delayed treatment of wounds of the hand and forearm under antibiotic cover.

In wounds of the hand and forearm treated within 4 h of injury, prophylactic clindamycin, in a dose of 150 mg 6-hourly for 5 days, did not reduce the infection rate. In wounds treated after 4 h the infection rate was reduced, but not significantly so. There was a significant reduction in the infection rate comparing all wounds treated within 4 h with those treated after 4 h. Early treatment of wounds is more important than prophylactic antibiotics, although these may have a part to play where late treatment is unavoidable.

Clindamycin↗
PubMed1980

Effects of toxicants on T-cell subpopulations as determined by lymphokine activity.

Selective depletion of T1 and T2 lymphocyte subpopulations of mouse spleens was accomplished by injecting mice subcutaneously with 5 mg cortisone acetate (CA) or 0.1 ml antithymocyte serum (ATS), respectively. Selectively depleted and control spleen cells were cultured in vitro and were tested for their ability to produce the lymphokine immune interferon (IIF) in response to the following mitogens: staphylococcal enterotoxin A (SEA), concanavalin A (ConA), and phytohaemagglutinin-P (PHA). The data indicate that SEA and PHA induce IIF from T1 and T2 cells respectively; ConA induces IIF from both T1 and T2 cells. Mice were also injected subcutaneously with 10 mg gallic acid (GA) and the pattern of mitogen-induction of IIF from GA-treated spleen cells was compared with that of CA- and ATS-treated spleen cells. GA pretreatment of mice, like CA pretreatment, resulted in a significant decrease in SEA-induced IIF; GA probably exerts its effect on T1 suppressor cells.

Animals↗
PubMed1980

Interferon immunosuppression: mediation by a suppressor factor.

Suppression of the in vitro antibody response to sheep erythrocytes by mouse fibroblast interferon occurred by induction of suppressor cell activity in spleen cells. The suppressor cells produced a soluble factor which mediated the immunosuppression. The suppressor factor did not inhibit virus replication; thus, interferon probably regulates the B-cell response by a mechanism that is different from its antiviral effect.

Animals↗