We hypothesize that Type II epithelial cells, which line the distal airspaces of the lung, are early responders to invading pathogens and release a signal, which activates and alters the phenotype and phagocytosis properties of alveolar macrophages even at a distance. The T(7) cell line is a conditionally immortalized murine Type II epithelial cell line developed in our laboratory. Using an in vitro transwell model we have previously shown that UV-irradiated Escherichia coli (UVEC)-stimulated T(7) cells cultured in the lower transwell chamber, release a diffusible signal which activates MH-S cells (immortalized murine alveolar macrophages) cultured in the upper transwell chamber, to produce nitric oxide. Using scanning electron microscopy, we show that MH-S cells activated in this manner exhibit increased cell surface ruffling, numerous long filopodia, increased lamellipodia and cell flattening. DynaBead uptake studies show that these morphologic changes are accompanied by increased phagocytosis. These findings indicate that a diffusible signal released at a distance by UVEC-stimulated Type II epithelial cells initiates changes in morphology and phagocytosis reflective of macrophage activation concomitant with the functional activation we previously reported.