Primary human alveolar epithelial cells can elicit the transendothelial migration of CD14(+) monocytes and CD3(+) lymphocytes

The ability of freshly isolated primary human alveolar epithelial cells (ty pe II pneumocytes) to induce leucocyte migration across an endothelial mono layer was investigated. Three-way factorial analysis of variance (ANOVA) de monstrated that resting alveolar endothelial cells (AEC) could produce dete ctable quantities of monocyte chemoattractant protein 1 (MCP-1), which was upregulated in response to tumour necrosis factor-alpha (TNF-alpha) in a do se- and time-dependent Fashion. Interferon-gamma (IFN-gamma) had no signifi cant effect on this process. TNF-alpha and IFN-gamma both induced AEC to pr ovoke migration of CD14(+) monocytes and CD3(+) lymphocytes across endothel ium. IFN-gamma and TNF-alpha synergized in their ability to induce producti on of T lymphocyte, but not monocyte, chemoattractants from AEC. Leucocyte transendothelial migration was inhibited by anti-MCP-1 neutralizing antibod y and by heparin, a polyanionic glycosaminoglycan (GAG). These data suggest that human AEC play a role in the multiple mechanisms that facilitate mono cyte and T lymphocyte migration into the alveolar compartment of the lung u nder homeostasis and inflammatory conditions. One of these mechanisms is me diated via constitutive MCP-I production by alveolar epithelial cells, whic h is upregulated by TNF-alpha.