[The effect of a short-term SO2 exposure on the respiratory function of sensitized non-anesthetized rabbits]. / Die Wirkung einer kurzzeitigen SO2-Exposition auf die Atemfunktion sensibilisierter nicht-narkotisierter Kaninchen.

Exposure to atmospheric pollutants may adversely effect respiratory function. Asthmatics as well as persons with airway hyperresponsiveness are more sensitive to atmospheric pollutants than normal persons. So we examined the influence of bovine serum albumin (BSA) sensitization on changes of respiratory function induced by SO2 exposure of 10 min. in non-anesthetized rabbits. Furthermore the effect of SO2-exposure on changes of respiratory function induced by secondary BSA-sensitization was tested. Respiratory flow (VR), tidal volume (Vt), respiratory pressure (PM), respiratory resistance (RL = PM/VR), and dynamic Compliance (Cdyn = Vt/PM) were examined. Our data showed that SO2-exposure marginally reduced respiratory flow and increased respiratory resistance but did not change tidal volume and dynamic compliance. Reduction of respiratory flow induced by SO2-exposure was independent from BSA-sensitization in the first week, however increase of respiratory resistance was slightly higher in BSA sensitized than in non-sensitized rabbits after SO2-treatment. Secondary BSA-sensitization reduced respiratory flow independent from SO2-inhalation and increased respiratory resistance stronger in SO2 treated than in non-treated rabbits. Tidal volume and dynamic compliance also increased after secondary sensitization. The increase of dynamic compliance was significantly higher in non-treated than in SO2 treated rabbits, but it was not so evident in case of tidal volume.

Non-specific airway responsiveness to hyperventilation of low doses of sulfur dioxide and cold air of non-smoking healthy volunteers of different ages.

We examined the effect of hyperventilation (HV) of sulfur dioxide (SO2)-air and cold air for 5 minutes on airway responsiveness of 37 (12 females and 25 males) healthy non-smoking volunteers of different ages. Body-plethysmographic measurements of airway resistance (Raw) and intrathoracic gas volume (ITGV) were performed before, 3, 10 and 20 mins. after the end of HV of SO2-air or cold air. Specific airway resistance (sRaw), product of Raw x ITGV, was used to evaluate the airway responsiveness. The mean (standard error) of percent changes of sRaw (delta %sRaw) were 121 (22), 45 (8) and 25 (4) at 3, 10 and 20 mins. after the end of HV of SO2-air. The corresponding values were 52 (8), 25 (5) and 19 (3) after HV of cold air. The differences in delta %sRaw between HV of SO2 and cold air were statistically significant (two sided t-test) for the 3 (p < 0.01) and 10 (p < 0.05) mins. values. Hyperventilation of SO2 and cold air produced delta sRaw above 100% in 14 (37.8%) and 5 (13.5%) volunteers, respectively. The difference in frequencies of delta sRaw above 100% between the HV of SO2 and cold air was statistically significant (p < 0.05, chi 2-Test). We observed a decreasing order of airway responsiveness with increasing age following HV of SO2 but not after cold air. We conclude that airway responsiveness to SO2 is poorly related to the response to cold air.

Modulation of murine T and B cell reactivity after short-term cadmium exposure in vivo.

This study assessed early effects of short-term Cd exposure on T and B cell responsiveness. Spleen cells from mice injected s.c. with a daily dosage of 1 mg, 0.33 mg, or 0.11 mg Cd (as CdCl2) per kg body weight for 5 days were examined for their potential to generate alloreactive T cells in a mixed lymphocyte reaction (MLR) and for mitogen reactivity to concanavalin A (Con A) in vitro. Spleen cells from the same mice were also assayed for the total number of IgM- and IgG-secreting B cells. Whereas alloreactivity was reduced, mitogen response to Con A was not different from controls or was even enhanced. The decrease in allogeneic MLR was dependent on the injected Cd dosage. No difference in susceptibility to Cd-induced effects was observed among the mouse strains tested, i.e. BALB/c, DBA/2, C57BL/6, and C3H/He. Co-cultivation of spleen cells, obtained from Cd-treated mice that exhibited deficient T cell reactivity, with splenic responder cells from untreated mice resulted in dose-dependent suppression of the normal MLR. These results indicate that the harmful effects of Cd on the immune system include the inhibition of antigen-specific T cell responses by the activation of an antigen non-specific suppressor system. In contrast to the suppressed allogeneic MLR, the same spleen cell populations showed augmented numbers of IgM- and IgG-antibody producing cells.

Metallothionein induction in a human B cell line by stimulated immune cell products.

Metallothionein (MT) is a protein inducible by heavy metals, various chemicals, immunomodulatory substances, and interleukins. We have asked the question whether immunostimulatory substances, such as lipopolysaccharide (LPS) or Concanavalin A (Con A), or supernatants obtained from human peripheral mononuclear cells (hPMC), which had been stimulated with LPS or Con A, are able to induce increased MT concentrations in cells of the immune system. For this purpose, the effects of LPS and Con A, and of supernatants obtained from immune cells stimulated by them were studied using the human IgM-secreting B cell line RPMI 1788. Supernatants obtained from hPMC that were stimulated by LPS or Con A increased the MT concentration in RPMI 1788 cells. However, LPS or Con A failed directly to increase MT concentrations in RPMI 1788 cells, whereas they increased MT concentrations in hPMC. Our data support the hypothesis that MT is probably not only important for metal homeostasis and protection against environmental hazards but also during immunostimulation.

[Are suppressor T-cells the primary target cells of lead immunotoxicity?]. / Sind Suppressor-T-Zellen die primären Zielzellen der immunotoxischen Wirkungen von Blei?

Studies were performed to investigate the effect of chronic low level lead exposure on the regulatory functions of T cells in the humoral immune response to sheep red blood cells (SRBC) in mice. Female mice were exposed to lead (as lead acetate) in the diet at 545 (group 1) and 2180 ppm (group 2) for 10 weeks. Lead exposure resulting in blood lead levels (PbB) of about 50 micrograms/100 g (group 1) produced a substantial increase of the number of IgG antibodies secreting spleen cells on days 3 and 4 after challenge. At the higher exposure level (group 2; PbB 60-80 micrograms/100 g) a suppression of the number of IgG plaque forming cells was observed. The IgM response was much smaller than the IgG response. Although differences between the group means were small, the results indicate that there also is an enhancement of the IgM response in the lower dosage group on days 3 and 4. In a second experiment the effect of in vivo lead exposure on antigenic competition was examined. Lead substantially reduced the effect of antigenic competition. Results of both experiments suggest that suppressor T cells rather than helper T cells may represent the primary target for lead. Throughout this study serum complement C3 levels were determined. Complement C3 levels tended to be reduced in the lead exposed groups before as well as after inocculation with SRBC.

Direct blockade of antigen-reactive B lymphocytes by immune complexes. An 'off' signal for precursors of IgM-producing cells provided by the linkage of antigen-and Fc-receptors.

Antigen-antibody complexes efficiently inhibit the induction of antibody formation. Using Mishell-Dutton cultures, it can be demonstrated that neither T cells nor their products are required for this inhibition of IgM PFC formation. The blockade is at the level of B cells and cannot be overcome by LPS or TRF. The data demonstrate that cross-linking of antigen- and Fc-receptors by antigen-antibody complexes is a blocking signal for B cells.