In vivo treatment of mice and hamsters with antibodies to asialo GM1 increases morbidity and mortality to pulmonary influenza infection.

The role of natural killer (NK) cells in host defenses against influenza virus infections in the lung was investigated by using rabbit antiserum to asialo GM1 (RAGM1), a neutral glycosphingolipid expressed on the plasma membrane of NK cells and some mouse pulmonary macrophages. Intravenous or intratracheal (i.t.) administration of RAGM1 resulted in depletion of the (in vitro) NK activity in lung and spleen or lung alone, respectively. The NK activity was depleted as early as 12 hr post-inoculation of antiserum, but returned to the normal range of activity by 4 days after antibody administration. RAGM1 serum treatment had no effect on the cytotoxic macrophage activity expressed by the plastic-adherent mononuclear cell populations isolated from mouse or hamster lung. Treatment of mice or hamsters with an i.t. or i.v. inoculation of RAGM1 rendered both species of laboratory animals susceptible to increased morbidity and mortality during a pulmonary influenza infection. These data support the hypothesis that a population of NK cells exist in an extravascular compartment within the lung, and that this local population of NK cells in the lung is crucial to the early natural pulmonary defenses during influenza infection.