Lymphokine-Induced Phenotypic Changes in Cells of a Type 2 Pneumocyte-Related Strain: Characterization of Activity in Mitogen-Stimulated Spleen Cell Supernatants

Abstract

Supernatants from concanavalin A-stimulated spleen cells contain a factor which induces morphological alterations, inhibition of replication, and altered phospholipid biosynthesis in cells of a type 2 pneumocyte-related strain designated NAL 1A. This study has demonstrated that the active factor is generated by nonadherent spleen cells in the presence of supernatants from cultures of stimulated adherent cells. The active factor inhibits proliferation of NAL 1A cells in a dose-dependent fashion, exerts an irreversible effect following overnight exposure of these cells to stimulated supernatants, and appears to be continuously synthesized by stimulated spleen cells in culture. It is stable at pH 2 for 4 hours, does not bind to Blue Sepharose CL-6B, and exhibits molecular heterogeneity on gel filtration chromatography, with maximal activity recovered infractions of molecular size 34,000 and 43,000. Comparable inhibition of growth was induced by exposure of NAL 1A cells to recombinant murine and human interleukin 2, as well as by recombinant murine interferon-gamma. These findings provide evidence for an interaction between type 2 pneumocytes and lymphokines such as interleukin-2 and interferon-gamma. The possible implications of a similar interaction occurring in vivo and its effects on type 2 pneumocyte morphology and function are discussed in the context of chronic interstitial inflammatory lung disease.