Lipopolysaccharide modulates the chemokine receptors CCR2 and CX3CR1 and induces recruitment of leukocytes to the central nervous system.

PERALTA RAMOS, JM; GAVIGLIO, EA; ARROYO, DS; BUSSI, C; IRIBARREN, P

Mar del Plata

Congreso; SAI / SAIC; 2014

SAI/SAIC

171. (293) LIPOPOLYSACCHARIDE MODULATES THE CHE-MOKINE RECEPTORS CCR2 AND CX3CR1 AND INDUCES RECRUITMENT OF LEUKOCYTES TO THE CENTRAL NERVOUS SYSTEMPeralta Ramos, Javier María; Gaviglio, Emilia Andrea; Arroyo, Daniela Soledad; Bussi, Claudio; Iribarren, Pablo Centro de Investigaciones en Bioquímica Clínica e Inmu-nología (CIBICI)-CONICET-UNC Microglial cells (MC) are components of the immune systemintrinsic to the central nervous system (CNS) and they participatein responses induced by infection, aseptic inflammation, injuryand/or neurodegeneration. These cells migrate to injury sites inresponse to chemoattractant agents that are produced under inflammatorycircumstances. This response greatly depends on theexpression and function of chemokine receptors. In this work, weevaluate the role of TLR4 in the regulation of the expression andfunction of chemoattractant receptors important in the recruitmentof phagocytes and neuroinflammation such as CCR2 and CX3CR1.First of all, the study of the modulation of chemokine receptorsin the CNS after a systemic pro-inflammatory stimulus with lipopolysaccharide(LPS), revealed a decreased gene expression ofCX3CR1 and CX3CL1 in mice total brain under these conditions(p<0,05). On the other hand, we evaluated the induction of neuroinflammation,activation of MC and recruitment of leukocytes tothe CNS. We observed an increase in the absolute number of MC,neutrophils, lymphocytes, dendritic cells and inflammatory monocytesin LPS-treated mice (p<0,001). Besides, we noted recruitedmonocytes showed CX3CR1 intracellularly and in the membrane,and intracellular CCR2, but only half of them expressed CCR2 inthe membrane (p<0,001). Similarly, although the majority of MCdisplayed CX3CR1 intracellularly and in the membrane, and mostof CCR2 was expressed intracellularly, only a low frequency ofthese cells exhibited this receptor in the membrane (p<0,001).Our results suggest that stimulation of TLR4 would induce theregulation of chemoattractant receptors which are key in therecruitment of leukocytes to the central nervous system and inthe neuroinflammatory response. Further research is merited todelineate the precise mechanisms underlying this modulation andwhich consequences would have over this response.