Acetylcholine and aceclidine reduce the mortality of mice after irradiation. This effect is evidently due to activation of M-cholinoreactive structures leading to an increase of the number of colony-forming units in the spleen, migration of T and B lymphocytes from lymphoid organs, and boosting of antibody production and of antibody-dependent cell cytotoxicity.
Key Words: ionizing radiation; immunocyte migration; antibody production; antibodydependent cell cytotoxicityRadioresistance is known to appreciably increase under the effect of cholinergic stimulation prior to irradiation [10]. There are different interpretations of the mechanisms lying at the basis of the radioprotective effect of cholinomimetics, but the immunological mechanisms of this phenomenon, specifically, during the use of cholinergic stimulants after irradiation, have been little studied. On the other hand, we know that agents stimulating M-cholinoreactive structures can activate some immune reactions [1,2,13]. Methods aimed at increasing radioresistance are based on the use of immunotropic agents (interleukin-1, tumor necrosis factor, etc.), which are used both before and after exposure [3]. This study was carded out to investigate the immunological mechanisms of radioresistance boost under the effect of cholinomimetics used after ionizing radiation.
MATERIALS AND METHODSExperiments were carded out with outbred and CBA mice weighing 18 to 22 g. Acetylcholine in a dose of 5 mg/kg three times a day and aceclidine in a single Toxicology Department, Saratov Medical Univemity dose of 1 mg/kg were used as cholinergic stimulants. The outbred animals were totally irradiated in a dose of 7 Gy. The lethality was assessed on day 9. Colony-forming splenocytes were determined by the endogenous colony formation method [7,15] aRer total exposure of outbred mice in a dose of 7 Gy.Migration of T cells from the thymus and of B lymphocy-tes from the bone marrow was assessed in CBA mice as described elsewhere [10], the index of migration being the content of antibody-producing cells in the spleens after 8 days, determined as described previously [ 12]. Cholinergic agonists were injected subcutaneously 30 to 60 min after exposure. Syngeneic T cells (2x107) or bone marrow cells (10 7 ) were administered simultaneously with sheep red cells (SRBC, 2x108) in a dose of 0.5 ml intravenously 1 day after irradiation. The migration of T and B cells was examined after exposure to 8 Gy with shielding of the thymus or hind limbs to the level of the knee joint, respectively. Antibody-producing cells in CBA mouse spleens were counted after 5 days as described previously [12] and antibody-dependent cell cytotoxicity (ADCC) was assessed in nonirradiated mice. These mice were immunized with sheep red cells (5x 10 s cells in 0.5 ml