Impact of ⁹⁰Sr on Mouse Natural Killer Cells and their Regulation by Alpha Interferon and Interleukin 2

Abstract

Male CBA/SU mice were exposed to ionizing radiation by intraperitoneal injection of the bone-seeking beta-emitter 90Sr. NK-cell lytic activities in spleen, peripheral blood, and lymph nodes were severely depressed or completely abolished. In contrast, production of the NK regulatory proteins alpha interferon (IFN-alpha) and interleukin 2 (IL-2) was normal 5-8 weeks after 90Sr injection. IFN-alpha, produced in vivo or in vitro by cells from injected mice, was able to enhance strongly NK lytic activities. These data indicate that 90Sr acts on the bone marrow, where it interferes with the maturation and seeding of NK precursor cells. The mechanisms regulating NK activities in peripheral organs remained relatively unchanged. Finally, we did not detect any major organ redistribution of NK cells as a result of 90Sr irradiation.

The role of natural killer cells in the early period of infection in murine cutaneous leishmaniasis

“…Recently, in mice with an intermittent suppression or depletion of NK cells by antiasialo GM1 or anti-NK1.1 monoclonal antibodies resulted in an increased susceptibility of mice to Leishmania major (5). previously described (6 The severe depletion of NK activity was confirmed by the lytic activity against YAC-1 cells in 90 Sr-treated animals ( Figure 1). The calculated number of cells required in control animals to obtain the same level of lysis of target cells as found in NK-depleted animals (i.e., 7% specific lysis) was shown to be 0.15 x 10 6 cells versus 2 x 10 6 spleen cells in NK-depleted animals.…”

Immune System Modifications Induced in a Mouse Model of Chronic Exposure to90Sr

“…Evidence from injection studies in animals corroborates the sensitivity of the immune system to radioactive strontium. In mice that have been injected with 89 Sr or 90 Sr to deplete bone marrow, NK cells are preferentially eliminated (Emmanuel et al 1981;Gidlund et al 1990;Haller and Wigzell 1977;Wiltrout et al 1989). The loss of this cell population results in a reduced ability to defend against lymphoid tumors (Haller and Wigzell 1977;Luevano et al 1981) or a transplanted methylcholanthrene-induced sarcoma (Scuderi and Rosse 1981b).…”

“…The loss of this cell population results in a reduced ability to defend against lymphoid tumors (Haller and Wigzell 1977;Luevano et al 1981) or a transplanted methylcholanthrene-induced sarcoma (Scuderi and Rosse 1981b). In CBA/SU mice injected with 90 Sr(NO 3 ) 2 , the responsiveness of spleen cells to activation by B-cell mitogen lipopolysaccharide was reduced, which was attributed to the cytotoxic effect of 90 Sr on bone marrow, a source of precursor cells for the spleen (Bierke 1990). In mice injected with 400-800 µCi 90 Sr/kg to deplete bone marrow, the thymus went through two phases of weight loss and regeneration within 50 days (Järplid 1973).…”

“…There appears to be a need for studies that examine the effect of a lower range of exposures on immune function. Another reason for such studies comes from the reports demonstrating that NK cells may be preferentially eliminated following injection of 89 Sr or 90 Sr (Emmanuel et al 1981;Gidlund et al 1990;Haller and Wigzell 1977;Wiltrout et al 1989), with the result that the organism's ability to defend against lymphoid tumors is impaired (Haller and Wigzell 1977;Luevano et al 1981). The implication is that reduced cellular defenses may compound the effect of genotoxicity, increasing the risk of cancer.…”

Effect of irradiation on hepatic natural killer cells

“…In most studies cytokines such as interleukin-2 and interferons or biological response modifiers have been used t o augment NK activity (7,8). Irradiation has been described to increase the cytotoxic potential of NK cells derived from the peripheral blood.…”