TY - JOUR
T1 - Expression of CXCL4 in microglia in vitro and in vivo and its possible signaling through CXCR3
AU - de Jong, Eiko K.
AU - de Haas, Alexander H.
AU - Brouwer, Nieske
AU - van Weering, Hilmar R. J.
AU - Hensens, Marjolein
AU - Bechmann, Ingo
AU - Pratley, Pierre
AU - Wesseling, Evelyn
AU - Boddeke, Hendrikus W. G. M.
AU - Biber, Knut
PY - 2008/6
Y1 - 2008/6
N2 - Signaling through chemokine receptor CXCR3 in the brain has been implicated in various brain diseases, as CXCR3 and its ligands are found under these conditions. Recently, a new chemokine ligand for CXCR3 was reported. In humans, an alternatively spliced variant of CXCR3 expressed on microvascular endothelial cells, named CXCR3b, was shown to bind CXCL4. In the periphery, the cellular expression and functions of CXCL4 are well described but in the brain its expression and function are unknown. Here, we show that brain microglia are a cellular source of CXCL4 in vitro and in vivo under neurodegenerating conditions. Microglial migration induced by CXCL4 is absent in CXCR3-deficient microglia, indicating a role of CXCR3. CXCL4 furthermore attenuates lipopolysaccharide-induced microglial phagocytosis and nitric oxide production in microglia and BV-2 cells. Based on these findings, it is proposed that locally released CXCL4 may control microglia responses.
AB - Signaling through chemokine receptor CXCR3 in the brain has been implicated in various brain diseases, as CXCR3 and its ligands are found under these conditions. Recently, a new chemokine ligand for CXCR3 was reported. In humans, an alternatively spliced variant of CXCR3 expressed on microvascular endothelial cells, named CXCR3b, was shown to bind CXCL4. In the periphery, the cellular expression and functions of CXCL4 are well described but in the brain its expression and function are unknown. Here, we show that brain microglia are a cellular source of CXCL4 in vitro and in vivo under neurodegenerating conditions. Microglial migration induced by CXCL4 is absent in CXCR3-deficient microglia, indicating a role of CXCR3. CXCL4 furthermore attenuates lipopolysaccharide-induced microglial phagocytosis and nitric oxide production in microglia and BV-2 cells. Based on these findings, it is proposed that locally released CXCL4 may control microglia responses.
KW - CNS
KW - CXCL4
KW - CXCR3
KW - microglia
KW - CENTRAL-NERVOUS-SYSTEM
KW - EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
KW - INTERFERON-INDUCIBLE PROTEIN-10
KW - CHEMOKINE RECEPTOR CXCR3
KW - IFN-GAMMA
KW - MULTIPLE-SCLEROSIS
KW - MOLECULAR CHARACTERIZATION
KW - LEUKOCYTE MIGRATION
KW - CUTTING EDGE
KW - ACTIVATION
U2 - 10.1111/j.1471-4159.2008.05267.x
DO - 10.1111/j.1471-4159.2008.05267.x
M3 - Article
VL - 105
SP - 1726
EP - 1736
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 5
ER -