IRIBARREN PABLO
Congresos y reuniones científicas
Título:
Lipopolysaccharide modulates the chemokine receptors CCR2 and CX3CR1 and induces recruitment of leukocytes to the central nervous system.
Autor/es:
PERALTA RAMOS, JM; GAVIGLIO, EA; ARROYO, DS; BUSSI, C; IRIBARREN, P
Lugar:
Mar del Plata
Reunión:
Congreso; SAI / SAIC; 2014
Institución organizadora:
SAI/SAIC
Resumen:
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 system
intrinsic to the central nervous system (CNS) and they participate
in responses induced by infection, aseptic inflammation, injury
and/or neurodegeneration. These cells migrate to injury sites in
response to chemoattractant agents that are produced under inflammatory
circumstances. This response greatly depends on the
expression and function of chemokine receptors. In this work, we
evaluate the role of TLR4 in the regulation of the expression and
function of chemoattractant receptors important in the recruitment
of phagocytes and neuroinflammation such as CCR2 and CX3CR1.
First of all, the study of the modulation of chemokine receptors
in the CNS after a systemic pro-inflammatory stimulus with lipopolysaccharide
(LPS), revealed a decreased gene expression of
CX3CR1 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 to
the CNS. We observed an increase in the absolute number of MC,
neutrophils, lymphocytes, dendritic cells and inflammatory monocytes
in LPS-treated mice (p<0,001). Besides, we noted recruited
monocytes showed CX3CR1 intracellularly and in the membrane,
and intracellular CCR2, but only half of them expressed CCR2 in
the membrane (p<0,001). Similarly, although the majority of MC
displayed CX3CR1 intracellularly and in the membrane, and most
of CCR2 was expressed intracellularly, only a low frequency of
these cells exhibited this receptor in the membrane (p<0,001).
Our results suggest that stimulation of TLR4 would induce the
regulation of chemoattractant receptors which are key in the
recruitment of leukocytes to the central nervous system and in
the neuroinflammatory response. Further research is merited to
delineate the precise mechanisms underlying this modulation and
which consequences would have over this response.
Microglial cells (MC) are components of the immune system
intrinsic to the central nervous system (CNS) and they participate
in responses induced by infection, aseptic inflammation, injury
and/or neurodegeneration. These cells migrate to injury sites in
response to chemoattractant agents that are produced under inflammatory
circumstances. This response greatly depends on the
expression and function of chemokine receptors. In this work, we
evaluate the role of TLR4 in the regulation of the expression and
function of chemoattractant receptors important in the recruitment
of phagocytes and neuroinflammation such as CCR2 and CX3CR1.
First of all, the study of the modulation of chemokine receptors
in the CNS after a systemic pro-inflammatory stimulus with lipopolysaccharide
(LPS), revealed a decreased gene expression of
CX3CR1 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 to
the CNS. We observed an increase in the absolute number of MC,
neutrophils, lymphocytes, dendritic cells and inflammatory monocytes
in LPS-treated mice (p<0,001). Besides, we noted recruited
monocytes showed CX3CR1 intracellularly and in the membrane,
and intracellular CCR2, but only half of them expressed CCR2 in
the membrane (p<0,001). Similarly, although the majority of MC
displayed CX3CR1 intracellularly and in the membrane, and most
of CCR2 was expressed intracellularly, only a low frequency of
these cells exhibited this receptor in the membrane (p<0,001).
Our results suggest that stimulation of TLR4 would induce the
regulation of chemoattractant receptors which are key in the
recruitment of leukocytes to the central nervous system and in
the neuroinflammatory response. Further research is merited to
delineate the precise mechanisms underlying this modulation and
which consequences would have over this response.
