HUMAN UPPER AIRWAY EPITHELIAL CELL-DERIVED GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR INDUCES HISTAMINE-CONTAINING CELL-DIFFERENTIATION OF HUMAN PROGENITOR CELLS

Nasal polyps and allergic rhinitis are upper airway inflammatory conditions characterized by increased numbers of eosinophils and metachromatic cells in the epithelial layer of the nasal mucosa. The objective of the current studies was to investigate the potential contribution of epithelial cells to the accumulation of inflammatory cells in the tissue. We have established pure cultures of human upper airway epithelial cells from normal and inflamed nasal polyps and allergic rhinitis tissue and examined the ability of conditioned medium from these cells (EpCM) to induce differentiation of human hemopoietic progenitors in vitro. We show that, under appropriate culture conditions, EpCMs, particularly those from cells derived from inflamed tissues. induce histamine-containing cell differentiation of cells of the human HL-60 myeloid leukemia cell line. These EpCMs also induce the emergence of both eosinophil/basophil and granulocyte/macrophage colonies in methylcellulose cultures of human peripheral blood mononuclear cells. We also show that CMs from epithelial cells derived from inflamed tissues contain greater amounts of granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to CMs from normal epithelial cells. Finally, we show that the histamine-containing cell differentiation of HL-60 cells as well as the colony growth induced by EpCM can be fully inhibited by preincubating this CM with a monoclonal neutralizing antibody to human GM-CSF. These studies: (a) illustrate the ability of human upper airway epithelial cells to secrete GM-CSF in vitro; (b) demonstrate differences between normal and inflamed tissue-derived epithelial cells, and (c) suggest that epithelial cells may, via the release of cytokines such as GM-CSF, contribute to the large tissue accumulation to inflammatory cells which characterizes nasal polyps, allergic rhinitis and, by extension, asthma.