REGULATION AND FUNCTION OF ADHESION MOLECULE EXPRESSION BY HUMAN ALVEOLAR EPITHELIAL-CELLS

The role of major histocompatibility complex (MHC) and adhesion molecu le expression by alveolar epithelium on the modulation of immune respo nses in the lung is not understood. We have developed efficient method s to isolate, purify and culture human alveolar epithelial cells (type II pneumocytes) in vitro. The expression of MHC and adhesion molecule s by isolated, cultured and cytokine-stimulated alveolar epithelial ce lls was quantified by flow cytometry, and demonstrated the presence of T-cell ligands including class I MHC, HLA-DR and HLA-DP, intracellula r adhesion molecule-1. (ICAM-1; CD54) and lymphocyte function-associat ed antigen (LFA-3; CD58), but not vascular cell adhesion molecule-1 (V CAM-1) (CD106) or B7 (CD80). The proinflammatory cytokine interferon-g amma (IFN-gamma) caused an up-regulation of class I MHC and ICAM-1. In contrast, tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) had little effect on the expression of these surface antigens by human alveolar epithelial cells. The functional activity o f alveolar epithelial adhesion molecules was then studied by determini ng their ability to bind allogeneic lymphocytes. An increase in lympho cyte adherence to monolayers of alveolar epithelial cells was observed following in vitro activation. However, up-regulation of alveolar epi thelial counter receptors with the proinflammatory cytokine gamma-IFN did not enhance adhesion. The adhesive interaction between CD18 on lym phocytes and ICAM-1 on alveolar epithelial cells was demonstrated by t he use of blocking antibodies specific for both ligands. Blockade of L FA-3 on alveolar monolayers also suppressed lymphocyte adherence. In c onclusion alveolar epithelial cells expressed MHC HLA-A,B,C, HLA-DR an d -DP, and functional adhesion molecules including ICAM-1 and LFA-3.