The Microenvironmental Differentiation Hypothesis of Airway Inflammation

Abstract

We have observed clinically relevant increases and fluctuations in metachromatic cell and eosinophil progenitors in response to antigenic challenge in patients with upper and lower respiratory tract disease. Based on this we have developed in vitro models to assess cytokine and microenvironmental influences on nasal mucosal inflammation. Purified structural cells (nasal epithelial cells or fibroblasts) grown from nasal polyps and atopic or nonatopic inferior turbinate secrete known (GM-CSF, G-CSF, and IL-6) and possibly novel (basophil differentiation factor) hemopoietic cytokines capable of inducing neutrophil, monocyte-macrophage, eosinophil, and metachromatic cell differentiation, as well as influencing their activation and survival. Nasal polyp structural cells are phenotypically different from those derived from allergic rhinitis or normal control subjects, having increased proliferative potential and constitutively producing higher levels of cytokines and extracellular matrices capable of supporting cell growth. These studies emphasize the importance of microenvironmental influences on allergic and nonallergic airway inflammation, and point out potentially new approaches to the diagnosis and therapy of nasal polyposis, allergic rhinitis, and asthma.