Mansfield, J. M. 1994. The induction of macrophage function during an immune response occurs in a multi-step pathway in which responsive cells require interaction with multiple stimuli for the full development of functional activity. The objective of our research is to identify the molecular genetic changes occurring during this activation pathway that are required for the development of macrophage tumor cell killing function. To approach this goal, our lab has produced a panel of molecular probes that recognize novel genes that are expressed only by macrophages capable of tumor cell killing. These studies have provided the first identification of molecular genetic changes occurring in activated macrophages committed to cytolytic activity.
Current work is focused in several areas.
First, the nature of the gene products identified by these probes is being characterized, as a first step to understanding the role of these products in the development and function of tumoricidal macrophages. Second, the regulatory regions that control macrophage-specific expression of these genes are being explored, to elucidate the mechanisms that control macrophage specific gene expression. Finally, in an experimental and clinical application of the work, the molecular probes are being used to characterize the activation profile of macrophages recruited to tumor sites in vivo . It is hoped the work ultimately will reveal target genes of importance that may be modified to control the macrophage component of the host response to neoplasia. Wynn, T. A., C. M. Nicolet, and D. M. Paulnock.