The focus of this laboratory is characterization of the phenotypic and functional features of mucosal macrophages. The major accomplishments of the past year include the following. 1.) We succeeded in routinely purifying lamina propria cells with morphologic and surface antigen features of macrophages. 2.) In addition to expressing accessory cell function, lamina propria macrophages were shown to secrete cytokines, including IL-1, which is necessary for successful antigen presentation, as well as TNF-alpha and TGF-beta. Gene expression studies suggested transcriptional regulation of the TNF-alpha peptide. 3.) We identified TNF-alpha mRNA in mucosal lesions associated with H. pylori gastritis and cytomegalovirus (CMV) colitis, suggesting a potential role for TNF- alpha in mediating mucosal inflammation. 4.) Relevant to CMV mucosal disease, we showed that CMV, but not HIV, primed monocytes for enhanced LPS-induced TNF-alpha secretion. In related studies, CMV infection of astrocytes was shown to induce TGF-beta, which then upregulated astrocyte expression of the virus. Whether a similar regulatory mechanisms applies to CMV expression by CMV-infected lamina propria macrophages will be pursued in future studies. 5.) We also demonstrated that lamina propria macrophages are capable of infection with HIV and that IgA may enhance this infection. 6.) Arachidonic acid metabolites were shown to be secreted by lamina propria macrophages, but not mucosal epithelial cells, in response to H. pylori. These studies implicate potentially important roles for lamina propria macrophages in mediating mucosal responses to mucosal pathogens and foreign antigens.
