Induction of glial L‐CCR mRNA expression in spinal cord and brain in experimental autoimmune encephalomyelitis

Abstract

Chemokines and chemokine receptors are important regulators of leukocyte trafficking and immune response. It is well established that chemokines and their receptors are also expressed in the central nervous system (CNS), where their expression has been associated with various neuroinflammatory diseases, such as multiple sclerosis (MS). One of the most important chemokines involved in MS pathology is CCL2 (previously known as MCP-1). CCL2, released by glial cells, activates the chemokine receptor CCR2, causing the infiltration of blood monocytes in tissues affected by MS. There is evidence, however, that CCL2 also has local effects on CNS cells, including induction or modulation of cytokine release and synthesis of matrix metalloproteinases, that might contribute to CNS pathology. These effects are most likely independent of CCR2, since CCR2 expression in glial cells is rarely observed. We have recently provided evidence for the presence of an alternative CCL2 receptor in glial cells called L-CCR and have investigated the expression of L-CCR mRNA in a murine EAE model. It is shown that L-CCR mRNA is expressed in infiltrating macrophages during EAE, but not in infiltrating T cells. Prominent expression of L-CCR mRNA was detected in astrocytes and microglia already at early time points throughout the brain and spinal cord supporting the hypothesis that L-CCR expression in glial cells is related to CNS inflammation.

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

“…Moreover, in previous studies, the use of anti-MCP-1 immunoneutralizing antibodies, or CCL2(−/−) astrocytes, failed to completely block microglial chemotaxis in response to conditioned medium from Tat-or morphine and Tat-exposed astrocytes . In addition, the absence of glial changes in CCR2(−/−) mice suggest that the alternative CCL2 receptor, L-CCR (Zuurman et al, 2003;Brouwer et al, 2004), is not involved. Collectively, the above findings suggest that an alternative CCR2 chemokine agonist, such as CCL12, is likely to have been acting together with CCL2 to enhance morphine and Tat-induced microglial chemotaxis in the absence of CCL2 in our earlier studies .…”

Essential Role of CCL2 in Clustering of Splenic ERTR-9+Macrophages during Infection of BALB/c Mice byListeria monocytogenes

“…The same reasoning might explain the differential survival of monocyte/ granulocyte populations with or without CCL2 depletion. On the other hand, CCL2 might signal in ERTR-9 ϩ macrophages via additional receptors, as described for astrocytes (4,37). Thus, depletion of CCL2 might influence ERTR-9 ϩ macrophages more severely than other cells.…”

Challenge with innate and protein antigens induces CCR7 expression by microglia in vitro and in vivo

“…For induction of experimental autoimmune encephalomyelitis (EAE), young adult (8-week old) female C57BL/ 6 mice were immunized with MOG peptide, as described previously (Amor et al, 1996;Brouwer et al, 2004). Immunization emulsions consisting of 200 mg MOG peptide (35-55) in incomplete Freund's adjuvants (IFA, Difco) and 80 mg killed mycobacteria (Difco) were injected subcutaneously on day 0 and 7.…”

“…The complex was visualized with streptavidin-FITC (1:100, Vector). GAPDH and CCR7 mRNA expression in sections of EAE brain and spinal cord was detected by a chromogenic detection method, using anti-DIG-AP (1:500, Roche), followed by an alkaline phosphatase color reaction (NBT/BCIP), as described previously (Brouwer et al, 2004). Coverslips were rinsed and mounted in Vectashield (Vector), before fluorescent microscopy analysis.…”

“…Therefore, we examined CCR7 expression at various disease stages. The development of EAE in C57BL/6 mice has been described previously (Brouwer et al, 2004). Briefly, mice developed symptoms of EAE 11 days after the first immunization.…”