Regulation of Natural Killer Cell Activity and Interferon Production in the Rat Lung Following Aerosol Challenge

Abstract

High levels of natural cytotoxicity were detected in vitro in cells from the lung interstitium of the rat following collagenase digestion of lung tissue. In contrast, alveolar cells exhibited negligible levels of natural cytotoxicity and furthermore suppressed the natural cytotoxicity of interstitial lung leukocytes. This suppression was alleviated following in vivo administration of indomethacin. The natural cytotoxicity of cells from both the lung and spleen was transiently suppressed following exposure of normal rats to aerosols of Escherichia coli lipopolysaccharide or of ovalbumin-sensitized rats to an ovalbumin aerosol. Parenchymal lung leukocytes, like those from the spleen and peripheral blood, showed enhanced cytotoxicity when treated with interferon in vitro. In addition interstitial leukocytes were capable of producing interferon when cocultured with P815 cells and, as was the case with the spleen, low density cells produced the most interferon. However, alveolar cells did not produce interferon in this system. These studies suggest that the lung is capable of self-regulation of the high levels of natural cytotoxicity present in interstitial tissue; alveolar cells or their products may suppress interstitial natural killer cells whilst interstitial leukocytes have the capacity to stimulate natural killer cells by producing interferon.