Tesis Doctorado
Activatión of pro-inflammatory functións in bovine neutrophils by store operated calcium entry (soce)
Autor
Burgos-A, Rafael
Universidad Austral de Chile
Institución
Resumen
Neutrophilic infiltration is an early process in acute inflammation. Pro-inflammatory functions in neutrophils, as in other non-excitable cells, is regulated by intracellular calcium concentrations [ Ca2+] i. One of the mechanisms that produce a raise in [Ca2+] i is the called Store OperatedCalcium Entry (SOCE). This investigation describes the effect of putative inhibitors of thismechanism as 2-aminophenylborate (2-APB), capsaicin, flufenamic acid and BTP2 in theoxidative and non-oxidative response in bovine neutrophils stimulated with platelet activationfactor (P AF). The first paper describes the effect of capsaicin, flufenamic acid and BTP2 o ver theROS production and MMP-9 release in bovine neutrophils. The second and third papers describethat 2-APB reduces the response induced by PAF in bovine neutrophils. We observed that 2-APB,without affecting cell viability and phagocyitc activity diminishes the reactive oxygen species(ROS) production, matrix metalloproteinase-9 (MMP-9), phosphatase alkaline activity, CD llbexpression in cell membrane, size changes of the cells and actin polymerization also, 2-APBincreases the L-selectin shedding in cell surface. The fourth paper describes that 2-APB has aninhibitory effect in zymosan-dependent ROS production in a CDllb-dependent manner. Finally, itis described for the first time the presence of Toll-like receptors (TLRs) mRNA -a family ofPathogen Recognition Receptors (PRRs)-. We were able to detect mRNA for TLRl, TLR2, TLR4,TLR6, TLR7 and TLRlO, but not for TLR3, TLRS, TLR8, TLR9 nor dectin-1. The fifth and lastchapter corresponds to a review about the regulation of neutrophil functions by intracellularcalcium concentration.