Distribution, cellular localization and functional role of CCR2 chemokine receptors in adult rat brain

Abstract

Recent studies demonstrated that the chemokine monocyte chemoattractant protein-1 (MCP-1)/CCL2 and its receptor, CCR2, play important roles in various brain diseases. In this study, using quantitative autoradiography, we studied the pharmacological properties of [125 I]MCP-1/CCL2 binding in rat brain and we clearly showed the distribution of CCR2 receptors in cerebral cortex, nucleus accumbens, striatum, amygdala, thalamus, hypothalamus, hippocampus, substantia nigra, mammillary bodies and raphe nuclei. Moreover, using double fluorescent immunohistochemistry, we showed that CCR2 receptors were constitutively expressed on neurons and astrocytes. Using RT-PCR methods, we demonstrated that CCR2 mRNA is present in various brain areas described above. Four hours after an acute intraperitoneal lipopolysaccharide injection, we showed that MCP-1/CCL2 binding was up-regulated in several brain structures; this effect took place on both CCR2B labelled neurons and astrocytes and to a lesser extent on activated microglia. To explore neurobiological function of CCR2, actimetric study was carried out. After intracerebroventricular injections of MCP-1/CCL2, we showed that motor activity was markedly decreased. Abbreviations used: BSA, bovine serum albumin; DEPC, diethylpirocarbonate; EAE, experimental autoimmune encephalomyelitis; FITC, fluorescein isothiocyanate; GFAP, glial fibrillary acidic protein; IL-1, interleukin-1; IL-8, interleukin-8; LPS, lipopolysaccharide; MCP-1, monocyte chemoattractant protein-1; MIP-1a, macrophage inflammatory protein-1a; MS, multiple sclerosis; PBS, phosphatebuffered saline; RANTES, regulated on activation normal T-cell expressed and secreted; SDF-1a, stromal cell-derived factor-1a; TARC, thymus and activation-regulated chemokine; TRITC, tetramethylrhodamine isothiocyanate.

CCR2 mediates increases in glial activation caused by exposure to HIV-1 Tat and opiates

“…Cells that express CCR2 in the CNS include macrophages/microglia, subpopulations of neurons and astrocytes (Simpson et al, 2000;Andjelkovic et al, 2002) and CCR2 expression is upregulated with inflammation (Banisadr et al, 2002;Mahad and Ransohoff, 2003).…”

Involvement of Pro- and Anti-Inflammatory Cytokines and Chemokines in the Pathophysiology of Traumatic Brain Injury

“…Expression of MCP-1 and its receptor CCR2 is rapidly increased in a wide range of cell types after acute brain injury. 82,83 Astrocytes, and to a lesser extent macrophages or fully reactive microglia, have been found to express MCP-1 following ischemia 84 and mechanical injury, 81 and CCR2 colocalized with activated microglia, 85 neurons, and astrocytes. 82 In addition to monocyte recruitment, there is direct evidence for the involvement of MCP-1 in driving acute inflammatory responses within the CNS, as well as indications that it may contribute to the pathogenesis of brain lesion development.…”

“…82,83 Astrocytes, and to a lesser extent macrophages or fully reactive microglia, have been found to express MCP-1 following ischemia 84 and mechanical injury, 81 and CCR2 colocalized with activated microglia, 85 neurons, and astrocytes. 82 In addition to monocyte recruitment, there is direct evidence for the involvement of MCP-1 in driving acute inflammatory responses within the CNS, as well as indications that it may contribute to the pathogenesis of brain lesion development. [85][86][87] In addition to MCP-1, the concentration of the chemokines MIP-1␣, MIP-2, and KC has been reported to increase following TBI in mouse brain.…”

Monocyte chemoattractant protein-1 has prosclerotic effects both in a mouse model of experimental diabetes and in vitro in human mesangial cells

“…In HMCs, the CCR2 receptor also mediates MCP-1-induced ICAM-1 levels [17]. Therefore, HMCs produce a functionally active CCR2 receptor as previously shown both in vitro [8][9][10][11][12] and in vivo [13][14][15]35] in other nonmononuclear cell types.…”

“…However, a functionally active CCR2 receptor has been demonstrated in other cell types both in vitro [8][9][10][11][12] and in vivo [13][14][15], suggesting that MCP-1 may have other functional effects beyond monocyte recruitment [16]. Accordingly, we recently reported that in human mesangial cells (HMCs) MCP-1 binding to CCR2 induces intercellular adhesion molecule-1 (ICAM-1) production, leading to enhanced monocyte adhesion [17].…”