PULMONARY SURFACTANT INHIBITS INTERLEUKIN-2-INDUCED PROLIFERATION ANDTHE GENERATION OF LYMPHOKINE-ACTIVATED KILLER-CELLS

The generation of lymphokine-activated killer (LAK) cell activity and the proliferative response to human recombinant interleukin-2 (IL-2) w ere significantly reduced when either human peripheral blood lymphocyt es (PBL) or purified CD56(+)/CD3(-) lymphocytes were cultured in the p resence of pulmonary surfactant. Surfactant concentrations ranging bet ween 30 and 500 mu g/ml produced increasing levels of-inhibition rangi ng from 20 to 95%. For any given concentration of surfactant, increasi ng the IL-2 concentration produced increasing levels of LAK activity b ut never overcame the suppressive effects of the surfactant. Time cour se studies demonstrated that surfactant is inhibitory only if added to PBL during the first 2 days of IL-2 culture, suggesting a preferentia l action during the induction phase of LAK activity. Pretreatment of P BL with surfactant for as little as 2 to 4 h inhibited their subsequen t response to IL-2 culture, suggesting that inhibition is rapid, persi stent, and directly due to alterations in PBL responsiveness. To deter mine if surfactant alters cell membrane function, we measured the effe cts of surfactant exposure on LAK:tumor binding. Binding of LAK cells to both K562 and M14 tumor targets was inhibited in a concentration-de pendent manner. Concurrently, we observed a reduced expression of IL-2 alpha-chain receptors on surfactant-treated CD56(+)/CD3(-) cells and a dramatic reduction in the expression of adhesion molecules including CD2, LFA-1, LFA-3, and ICAM-1. We conclude that pulmonary surfactant has the potential to suppress cytotoxic and proliferative responses to IL-2, alters cell-to-cell interactions, and reduces the expression of activation and adhesion molecules on LAK cells.