Athymic nude rat. III natural cell mediated cytotoxicity.

Homozygous rnu/rnu and heterozygous +/rnu rats were investigated and compared with each other for the existence of natural cell-mediated cytotoxicity. Investigated were total, adherent, and nonadherent cell populations from spleen, peritoneal cavity, and mesenteric lymph node. The natural killer (NK) cell activity was measured in a 4-hr 51Cr-release assay with a xenogeneic murine YAC lymphoma target cell line. In both and +/rnu rats the peritoneal cavity had the highest percentage of activity, while the spleen and mesenteric lymph node showed a lower activity. The mesenteric lymph node of +/rnu rats of 8–10 weeks of age was found to express a very low activity, in contrast to a very high activity in rats. For almost every effector to target cell (E:T) ratio investigated (100, 70, 50, and 10), the natural killer cell activity in the nude rats was found to be significantly higher than in their thymus-bearing littermates. In comparison with that of +/rnu rats, NK activity in the nonadherent cell fractions of athymic rats was 50 to 60% higher in spleen cells, doubled in peritoneal cells, and increased 10-fold or higher in lymph node cells. Investigations o

Critical factors for liposome-incorporated tumour-associated antigens to induce protective tumour immunity to SL2 lymphoma cells in mice

Physical and immunogenic properties of re- constituted membranes designed for the presentation of tumour-associated antigens (TAA) to the immune system are described. Proteins and lipids of crude membranes of SL2 routine lymphosarcoma cells were partially solubi- lized with octylglucoside. Reconstituted membranes, con- sisting mainly of unilamellar vesicles with a diameter of 0.03-0.15 gm, were formed by detergent removal and were purified by floatation in a discontinuous sucrose gra- dient to remove non-lipid-bound protein. Subcutaneous immunization of syngeneic mice with reconstituted mem- branes or with purified reconstituted membranes induced protection against an intraperitoneal challenge with 103 viable SL2 cells. Reconstituted membranes were more im- munogenic than crude membranes in immunoprotection experiments when compared on the basis of protein dose. Detergent removal was required to obtain an immunogenic presentation form of SL2 membrane antigens and to avoid toxicity associated with the detergent. Reconstitution of SL2 membranes in the presence of exogenous phos- pholipid slightly increased the fraction of protein that as- sociated with the reconstituted membranes. However, the immunogenicity of the solubilized membrane TAA was not significantly affected by the presence of exogenous phospholipid. The reconstitution procedure described may be useful in identifying membrane factors required for the induction of immune responses against TAA. The versatil- ity of the system may be employed to develop safe alterna- tives for whole-cell vaccines

No adaptation to UV-induced immunosuppression and DNA damage following exposure of mice to chronic UV-exposure

It is well known that ultraviolet (UV) radiation induces erythema, immunosuppression and carcinogenesis. We hypothesized that chronic exposure to solar UV radiation induces adaptation that eventually prevents the suppression of acquired immunity. We studied adaptation for UV-induced immunosuppression after chronic exposure of mice to a suberythemal dose of solar simulated radiation (SSR) with Cleo Natural lamps, and subsequent exposure to an immunosuppressive dose of solar or UVB radiation (TL12). After UV dosing, the mice were sensitized and challenged with either diphenylcyclopropenone (DPCP) or picryl chloride (PCl). To assess the adaptation induced by solar simulated radiation, we measured the proliferative response and cytokine production of skin-draining lymph node cells after immunization to DPCP, the contact hypersensitivity (CHS) response to PCl, and thymine-thymine (T-T) cyclobutane dimers in the skin of mice. After induction of immunosuppression by SSR or by TL12 lamps, the proliferative response of draining lymph node cells after challenge with DPCP, or the CHS after challenge with PCl, showed significant suppression of the immune response. Chronic irradiation from SSR preceding the immunosuppressive dose of UV failed to restore the suppressed immune response. Reduced lipopolysaccharide-triggered cytokine production (of IL-12p40, IFN-gamma, IL-6 and TNF-alpha) by draining lymph node cells of mice sensitized and challenged with DPCP indicated that no adaptation is induced. In addition, the mice were not protected from T-T dimer DNA damage after chronic solar irradiation. Our studies reveal no evidence that chronic exposure to low doses of SSR induces adaptation to UV-induced suppression of acquired immunity

Targeted delivery of diphtheria toxin via immunoliposomes: efficient antitumor activity in the presence of inactivating anti-diphtheria toxin antibodies

AbstractDiphtheria toxin (DT) has attracted considerable attention for anti-cancer therapy. However, its extensive use is prohibited by (i) its non-specific action which can result in substantial toxicity, (ii) most patients have low serum levels of anti-DT antibodies (AT antibodies) which can inactivate DT and (iii) its immunogenicity will boost the circulating AT antibody level, thereby further compromising the antitumor activity. To overcome these limitations, we have developed a new approach for targeted delivery of DT utilizing immunoliposomes. In this approach, protection against the non-specific action of DT is combined with efficient antitumor activity even in the presence of inactivating AT antibodies

Traffic-related air pollutants induce the release of allergen-containing cytoplasmic granules from grass pollen

International audienceBackground/Aim: Pollen cytoplasmic granules (PCG) are loaded with allergens. They are released from grass pollen grains following contact with water and can form a respirable allergenic aerosol. On the other hand, the traffic-related air pollutants NO2 and O-3 are known to be involved in the current increase in the prevalence of allergic diseases via their adjuvant effects. Our objective was to determine the effects of air pollutants on the release of PCG from Phleum pratense (timothy grass) pollen. Methods: P. pratense pollen was exposed to several concentrations of NO2 and O-3. The induced morphological damages were observed by environmental scanning electron microscopy, and the amount of PCG released from the pollen upon contact with water was measured. Results: The percentages of damaged grain were 6.4% in air-treated controls, 15% after treatment with the highest NO2 dose (50 ppm) and 13.5% after exposure to 0.5 ppm O-3. In treated samples, a fraction of the grains spontaneously released their PCG. Upon subsequent contact with water, the remaining intact grains released more PCG than pollen exposed to air only. Conclusions: Traffic-related pollutants can trigger the release of allergen-containing granules from grass pollen, and increase the bioavailability of airborne pollen allergens. This is a new mechanism by which air pollution concurs with the current increase in the prevalence of allergic diseases

Liposomes as a drug carrier system for cis-diamminedichloroplatinum (II). I. Binding capacity, stability and tumor cell growth inhibition in vitro

We investigated the potential of liposomes as drug carrier for cis-diamminedichloroplatinum(II) (cis-DDP). The binding capacity, Pt release on storage, and in vitro antitumor activity was determined. It was found that the encapsulation efficiency was dependent on the NaCl concentration of the hydration medium in which cis-DDP was dissolved. In addition, cis-DDP liposomes prepared by hydration with 0.9% NaCl showed a relatively high drug leakage on storage. For cis-DDP liposomes prepared by hydration with 0.2% NaCl/4.2% mannitol or 5% mannitol the fraction of the drug associated with the liposomes was more than 90% after prolonged storage at 4°C for 50 days. Compared to the activity of free cis-DDP, cis-DDP encapsulated in liposomes showed a decreased antitumor activity in vitro against a murine gastric squamous cell carcinoma. This suggested that the antitumor activity of liposomal cis-DDP was due to leakage of cisDDP from the liposomes. However, cis-DDP recovered from PC/PS/Chol liposomes after 3 cycles of freezing and thawing was equally active as free cisDDP. From the present study it is concluded that cisDDP liposomes prepared by hydration with 5% mannitol or 0.2% NaCl/4.2% mannitol have a relatively high binding capacity, and high stability against drug leakage