Substance P receptor mediated macrophage responses.

Taken together, these studies demonstrate an important role for substance P receptor expression by macrophages. The results to date suggest proinflammatory signals mediated by this receptor, and it is clear that substance P can act synergistically with other factors to stimulate macrophage activity. Antagonism of substance P/substance P receptor interactions in vivo profoundly affect immunity against Salmonella. This model provides evidence that an optimal host response against this intracellular pathogen of macrophages requires signaling through the substance P receptor. The ability of interferon gamma or IL-4 to upregulate substance P receptor mRNA expression on macrophages suggests that substance P-mediated amplification loops might involve either T helper type 1 or T helper type 2 responses. Thus, depending upon the immunologic stimulus, substance P could contribute to cell mediated as well as humoral immune responses. Several important questions remain. Since the antigen processing and presenting function is an important macrophage activity, the effect of signaling through the substance P receptor on these events has not been defined. Furthermore, since macrophages are only one type of antigen presenting cell, it will be important to determine the role of substance P receptor expression in the activity of dendritic cells. We anticipate that these ongoing investigations will further define the positive contributions that substance P/substance P receptor interactions have in the initiation of immune responses.