Activation of Peritoneal Macrophages with Human Cholesteatoma Debris and α-Keratin

The effect of human cholesteatoma debris on mouse peritoneal macrophages was studied in vivo. The number of macrophages and lymphocytes increased 5 days after injection of the debris into the peritoneal cavity. A similar increase in peritoneal cells was observed when an urea-extracted fraction of the cholesteatoma debris or α-keratin, a major component of the debris, was injected. Both cholesteatoma debris- and α-keratin-elicited macrophages exhibited a greater response of luminol-dependent chemiluminescence upon exposure to zymosan, suggesting that the elicited macrophages were activated. In contrast, other constituents of the debris, such as cholesterol or fatty acid-with the exception of lipopolysaccharide (LPS)-failed to elicit or activate peritoneal macrophages at the similar doses detected in the debris. The chemiluminescent response of macrophages obtained by injecting LPS was, however, much lower than that of a-keratin-induced macrophages. These results indicate that cholesteatoma debris is capable of eliciting and activating macrophages, and that α-keratin is responsible for the activation.