DMPD: Dynamic Macrophage Pathway Database

The immune system has evolved as a defense mechanism against pathogenic microbes [3]. The immune system is closely connected with the hematologic system since white blood cells are key players in the lymphoid system. Cellular participants in the immune and inflammatory responses include antigen presenting cells and phagocytic cells, such as macrophages. Significant progress has been made recently in understanding the biochemical mechanisms by which lipopolysaccharide (LPS), a bacterial endotoxin, activates immune cells, particularly macrophages [4]. Macrophage over-reaction to the presence of LPS can lead to sepsis, septic shock, or systemic inflammatory response syndrome due to production of a variety of inflammatory cytokines by activated macrophages. It is well-known that macrophages stimulated with LPS release tumor necrosis (TNF) and interleukins (IL-1, IL-6, IL-8 and IL-12) [1] which are important mediators of sepsis syndrome and the response to Gram-negative bacterial infections. Increasing evidence suggests that monocytic cell from patients with sepsis and septic shock survivors have characteristics of LPS tolerance and a profoundly altered response to LPS. Despite much effort, unfortunately there is no effective therapy for this problem. It is estimated that around 50,000 people die each year in the United States of septic shock or systemic inflammatory syndrome [2]. Thus, a more detailed understanding of the molecular mechanisms underlying activation and deactivation of macrophages in response to LPS becomes crucial for the development of novel therapies for septic shock and the treatment of septic shock survivors [6].