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Neutrophilic polymorphonuclears (PMNs) play an important role in the progression of sepsis-related inflammation and become highly activated by a wide array of ligands on the site. The triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently described receptor that has many effects on human PMN. The engagement of TREM-1 on PMN can induce phagocytosis, reactive oxygen species production and release of myeloperoxidase and IL-8. LPS has a priming effect on these functions. We show in this paper that Lyn, AKT, extracellular signal-regulated kinase 1/2 and Jak2 signaling pathways are elicited following TREM-1 engagement and activation by a monoclonal agonist antibody (anti-TREM-1) in human PMN, leading to the phosphorylation of STAT5 and RelA, a subunit of the nuclear factor-kappa B family. We also show that TREM-1 is recruited to ganglioside M1-lipid rafts in PMN upon stimulation with LPS or anti-TREM-1. Moreover, we observed that Toll-like receptor 4 and TREM-1 co-localize upon stimulation and TREM-1 engagement resulted in the phosphorylation of IL-1R-associated kinase 1, but not its stimulant-induced degradation. These data shed a new light on how various receptors implicated in the innate immune response could interact to insure an efficient inflammatory response upon pathogens-associated aggression. [ABSTRACT FROM AUTHOR]

AbstractHuman neutrophils are activated by a wide array of compounds through their receptors. This elicits their classical functions, such as chemotaxis, phagocytosis, and the production of reactive oxygen species (ROS). Upon stimulation, neutrophils also produce lipid and immune mediators and can present antigen through the major histocompatibility complex I (MHC-I). The age-related impairment of the classical functions of neutrophils is well described, but experimental evidence showing alterations in the production of mediators and antigen presentation with aging are lacking. This review highlights the role of neutrophils in age-related pathologies such as Alzheimer's disease, atherosclerosis, cancer, and autoimmune diseases. Furthermore, we discuss how aging potentially affects the production and release of mediators by human neutrophils in ways that may contribute to the development of these pathologies. [ABSTRACT FROM AUTHOR]