The t-SNARE syntaxin 4 is regulated during macrophage activation to function in membrane traffic and cytokine secretion

Activation of macrophages with lipopolysaccharide (LPS) induces the rapid synthesis and secretion of proinflammatory cytokines, such as tumor necrosis factor (TNFalpha), for priming the immune response [1, 2]. TNFalpha plays a key role in inflammatory disease [3]; yet, little is known of the intracellular trafficking events leading to its secretion. In order to identify molecules involved in this secretory pathway, we asked whether any of the known trafficking proteins are regulated by LPS. We found that the levels of SNARE proteins were rapidly and significantly up- or downregulated during macrophage activation. A subset of t-SNAREs (Syntaxin 4/SNAP23/Munc18c) known to control regulated exocytosis in other cell types [4, 5] was substantially increased by LPS in a temporal pattern coinciding with peak TNFalpha secretion. Syntaxin 4 formed a complex with Munc18c at the cell surface of macrophages. Functional studies involving the introduction of Syntaxin 4 cDNA or peptides into macrophages implicate this t-SNARE in a rate-limiting step of TNFalpha secretion and in membrane ruffling during macrophage activation. We conclude that in macrophages, SNAREs are regulated in order to accommodate the rapid onset of cytokine secretion and for membrane traffic associated with the phenotypic changes of immune activation. This represents a novel regulatory role for SNAREs in regulated secretion and in macrophage-mediated host defense.

Local colours for Indonesian National police

As a result of the local autonomy program that commenced in Indonesia in Jan 2001, there is a concern regarding the applicability of the formalized model of security & the possibility of that being replaced by a local community-based security model. This rather informal security model is then promoted to be the only form of security used between societies & the nation. However, this model does not solve the problem because of widespread corruption, collusion, & nepotism, & the many limitations of the Indonesian National Police (Polri), a police department that has a mediocre & generalized level of service. In relation to autonomy, the effort of empowering the police units from the regional police down will bridge the gap between the people's ability to protect themselves & the limitations of those that are sworn to uphold the law. 17 References. Adapted from the source document.