Complement receptor-positive microglia at the expanding grey matter lesion edge
Author(s): ,
R. Evans
Affiliations:
Swansea University Medical School, Swansea
,
L. Watkins
Affiliations:
Swansea University Medical School, Swansea
,
M. Rees
Affiliations:
Swansea University Medical School, Swansea
,
P. Morgan
Affiliations:
Cardiff University School of Medicine, Cardiff
,
D. Fathalla
Affiliations:
Cardiff University School of Medicine, Cardiff
,
M. Naughton
Affiliations:
School of Medicine, Dentistry and Biomedical Sciences, Belfast, United Kingdom
,
D. Fitzgerald
Affiliations:
School of Medicine, Dentistry and Biomedical Sciences, Belfast, United Kingdom
,
J. Neal
Affiliations:
Cardiff University School of Medicine, Cardiff
O. Howell
Affiliations:
Swansea University Medical School, Swansea
ECTRIMS Online Library. Evans R. Oct 12, 2018; 228897; P1056
Rhian Evans
Rhian Evans
Contributions
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Abstract

Abstract: P1056

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Pathology

Introduction: Cortical grey matter lesions (GMLs) are an important determinant of neurological disability in progressive multiple sclerosis (MS). Our understanding of the mechanisms of GML pathogenesis are incomplete, but we and others have shown a role for increased microglial and complement activation. Microglia express receptors to pro-inflammatory complement anaphylatoxins (e.g. C5a receptor (C5aR)), and we are interested in the relationship between complement-mediated microglial activation and GML pathology in progressive MS.
Aims: We aimed to characterise the phenotype of complement receptor expressing microglia in association with pathological features of GMLs.
Methods: We performed quantitative and morphological analysis of complement receptor-positive microglia in GMLs of 20 post-mortem progressive MS cases and 13 non-neurological disease controls (research ethics approval 13/WA/0292).
Results: Microglia/macrophages positive for C5aR were significantly increased at the expanding GML edge, compared to normal appearing tissue and controls (p< 0.05). C5aR+ microglia/ macrophages closely opposed neurons immunopositive for complement activation products and were in contact with damaged axons (SMI-32+) and disrupted myelin. In the MS cortex, microglia/macrophages expressed TNF-α and iNOS, and were larger in area (p=0.035) and more round (p=0.013) at the expanding lesion edge. Alterations in morphology are indicative of microglial activation, and we have replicated this change in a cortical microglial cell line in response to classic pro-inflammatory mediators (more round, p< 0.0001). We now aim to explore the anaphylatoxin-mediated microglial activation in vitro to determine how these cells might affect myelin and neuron integrity in MS.
Conclusions: Microglia/macrophages expressing C5aR are increased at the GML edge. Complement activation and the generation of pro-inflammatory anaphylatoxins such as C5a, may drive a neurotoxic microglial reaction, which will contribute to cortical pathology in progressive MS.
Disclosure: Rhian Evans: Nothing to disclose; Lewis Watkins: Nothing to disclose; Mark Rees: Nothing to disclose; Paul Morgan: Nothing to disclose; Dina Fathalla: Nothing to disclose; Michelle Naughton: Nothing to disclose; Denise Fitzgerald: Nothing to disclose; James Neal: Nothing to disclose; Owain Howell: Nothing to disclose.

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