Pulmonary surfactant inhibits interleukin-2-induced proliferation and the 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) were significantly reduced when either human peripheral blood lymphocytes (PBL) or purified CD56+/CD3- lymphocytes were cultured in the presence of pulmonary surfactant. Surfactant concentrations ranging between 30 and 500 micrograms/ml produced increasing levels of inhibition ranging from 20 to 95%. For any given concentration of surfactant, increasing the IL-2 concentration produced increasing levels of LAK activity but never overcame the suppressive effects of the surfactant. Time course studies demonstrated that surfactant is inhibitory only if added to PBL during the first 2 days of IL-2 culture, suggesting a preferential action during the induction phase of LAK activity. Pretreatment of PBL with surfactant for as little as 2 to 4 h inhibited their subsequent response to IL-2 culture, suggesting that inhibition is rapid, persistent, and directly due to alterations in PBL responsiveness. To determine if surfactant alters cell membrane function, we measured the effects of surfactant exposure on LAK:tumor binding. Binding of LAK cells to both K562 and M14 tumor targets was inhibited in a concentration-dependent 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.
Roth
M D
MD
Division of Pulmonary Medicine, UCLA School of Medicine 90024.
Pinto
M
M
Golub
S H
SH
Shau
H
H
D000328:Adult; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000502:physiology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D011663:Pulmonary Surfactants / Q000502:physiology*; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D011663:Pulmonary Surfactants