Contributions
Abstract: P416
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Pathology
White-matter demyelination in Multiple Sclerosis (MS) is accompanied by a dysfunctional blood-brain-barrier leading to infiltration of leukocytes into the central nervous system (CNS). In post-mortem material of MS patients, these leukocytes and additional amoeboid-shaped, activated, microglia are present in white-matter lesions (WMLs). However, grey-matter lesions (GMLs) are almost devoid of infiltrating leukocytes and show only a modest microglial reaction. This clear difference in microglial reaction between WMLs and GMLs has raised questions about the responsivity of WM and GM-derived microglia in MS pathology.
In the present study, primary human microglia cultured from post-mortem MS patient-derived subcortical white- and cortical grey-matter were used to investigate the expression of microglia specific proteins TMEM119 and P2RY12 upon treatment of the cells with the pro-inflammatory stimuli IFN-γ+LPS, or with the anti-inflammatory cytokine IL-4. In addition, we studied TMEM119, P2RY12, IFN-γ and IL-4 immunoreactivity in human post-mortem MS WMLs and subpial GMLs.
TMEM119 and P2RY12 mRNA levels in human primary microglia were down-regulated when cells were treated with IFN-γ+LPS. In addition, P2RY12 mRNA level was enhanced when stimulated with IL-4, whereas TMEM119 mRNA level was equal to control. These responses were similar in white matter derived microglia and in grey matter derived microglia. In addition, this pattern of mRNA regulation was reflected in TMEM119 and P2RY12 immunoreactivity in WMLs where, if CD3 and CD20 positive lymphocytes, and IFN-γ positive cells were present, less TMEM119 and P2RY12 immunoreactivity was present. When lymphocytes and IL-4 immuno-positive cells were present, P2RY12 immunoreactivity could be observed, but not TMEM119. In subpial GMLs, where infiltration of leukocytes, including lymphocytes, and IL-4 and IFN-γ immune-positive cells were absent, TMEM119 and P2RY12 immunoreactivity was similar to normal appearing white and grey matter.
These results suggest that the difference in microglial response in demyelinating WMLs and GMLs could be driven by the presence or absence of leukocytes, respectively. Further studies to determine the microglial subtypes present in WMLs and GMLs, are warranted.
Disclosure: Thecla A. van Wageningen: Nothing to disclose, Kees A. Jongenelen: Nothing to disclose, John G.J.M. Bol: Nothing to disclose, Anne-Marie van Dam: Nothing to disclose
This study is financially supported by the Dutch MS Research Foundation (grant nr 15-904MS)
Abstract: P416
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Pathology
White-matter demyelination in Multiple Sclerosis (MS) is accompanied by a dysfunctional blood-brain-barrier leading to infiltration of leukocytes into the central nervous system (CNS). In post-mortem material of MS patients, these leukocytes and additional amoeboid-shaped, activated, microglia are present in white-matter lesions (WMLs). However, grey-matter lesions (GMLs) are almost devoid of infiltrating leukocytes and show only a modest microglial reaction. This clear difference in microglial reaction between WMLs and GMLs has raised questions about the responsivity of WM and GM-derived microglia in MS pathology.
In the present study, primary human microglia cultured from post-mortem MS patient-derived subcortical white- and cortical grey-matter were used to investigate the expression of microglia specific proteins TMEM119 and P2RY12 upon treatment of the cells with the pro-inflammatory stimuli IFN-γ+LPS, or with the anti-inflammatory cytokine IL-4. In addition, we studied TMEM119, P2RY12, IFN-γ and IL-4 immunoreactivity in human post-mortem MS WMLs and subpial GMLs.
TMEM119 and P2RY12 mRNA levels in human primary microglia were down-regulated when cells were treated with IFN-γ+LPS. In addition, P2RY12 mRNA level was enhanced when stimulated with IL-4, whereas TMEM119 mRNA level was equal to control. These responses were similar in white matter derived microglia and in grey matter derived microglia. In addition, this pattern of mRNA regulation was reflected in TMEM119 and P2RY12 immunoreactivity in WMLs where, if CD3 and CD20 positive lymphocytes, and IFN-γ positive cells were present, less TMEM119 and P2RY12 immunoreactivity was present. When lymphocytes and IL-4 immuno-positive cells were present, P2RY12 immunoreactivity could be observed, but not TMEM119. In subpial GMLs, where infiltration of leukocytes, including lymphocytes, and IL-4 and IFN-γ immune-positive cells were absent, TMEM119 and P2RY12 immunoreactivity was similar to normal appearing white and grey matter.
These results suggest that the difference in microglial response in demyelinating WMLs and GMLs could be driven by the presence or absence of leukocytes, respectively. Further studies to determine the microglial subtypes present in WMLs and GMLs, are warranted.
Disclosure: Thecla A. van Wageningen: Nothing to disclose, Kees A. Jongenelen: Nothing to disclose, John G.J.M. Bol: Nothing to disclose, Anne-Marie van Dam: Nothing to disclose
This study is financially supported by the Dutch MS Research Foundation (grant nr 15-904MS)