Abstract |
Lysophosphatidylcholine (LPC) is a chemotactic lysolipid produced during inflammation by the hydrolytic action of phospholipase A(2) enzymes. LPC stimulates chemotaxis of T cells in vitro through activation of the G protein-coupled receptor, G2A. This has led to the proposition that G2A contributes to the recruitment of T cells to sites of inflammation and thus promotes chronic inflammatory autoimmune diseases associated with the generation and subsequent tissue infiltration of auto- antigen-specific effector T cells. However, one study suggests that G2A may negatively regulate T cell proliferative responses to antigen receptor engagement and thereby attenuates autoimmunity by reducing the generation of autoreactive T cells. To address the relative contribution of these G2A-mediated effects to the pathophysiology of T cell-mediated autoimmune disease, we examined the impact of G2A inactivation on the onset and severity of murine experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). Wild type (G2A(+/+)) and G2A-deficient (G2A(-/-)) C57BL/6J mice exhibited a similar incidence and onset of disease following immunization with MOG(35-55) peptide. Disease severity was only moderately reduced in G2A(-/-) mice. Similar numbers of MOG(35-55) specific T cells were generated in secondary lymphoid organs of MOG(35-55)-immunized G2A(+/+) and G2A(-/-) mice. Comparable numbers of T cells were detected in spinal cords of G2A(+/+) and G2A(-/-) mice. We conclude that the proposed anti-proliferative and chemotactic functions of G2A are not manifested in vivo and therefore therapeutic targeting of G2A is unlikely to be beneficial in the treatment of MS.
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Authors | Inga Osmers, Sherry S Smith, Brian W Parks, Shaohua Yu, Roshni Srivastava, Jillian E Wohler, Scott R Barnum, Janusz H S Kabarowski |
Journal | Journal of neuroimmunology
(J Neuroimmunol)
Vol. 207
Issue 1-2
Pg. 18-23
(Feb 15 2009)
ISSN: 0165-5728 [Print] Netherlands |
PMID | 19135725
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Cell Cycle Proteins
- G2A receptor
- Glycoproteins
- Myelin-Oligodendrocyte Glycoprotein
- Peptide Fragments
- Receptors, G-Protein-Coupled
- myelin oligodendrocyte glycoprotein (35-55)
- Interferon-gamma
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Topics |
- Animals
- CD4-Positive T-Lymphocytes
(immunology)
- CD8-Positive T-Lymphocytes
(immunology)
- Cell Cycle Proteins
(genetics, physiology)
- Cell Proliferation
(drug effects)
- Encephalomyelitis, Autoimmune, Experimental
(chemically induced, genetics, immunology)
- Flow Cytometry
(methods)
- Gene Deletion
- Glycoproteins
(adverse effects)
- Interferon-gamma
(metabolism)
- Lymph Nodes
(drug effects, immunology, pathology)
- Lymphocyte Activation
(genetics, immunology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Myelin-Oligodendrocyte Glycoprotein
- Peptide Fragments
(adverse effects)
- Receptors, G-Protein-Coupled
(deficiency, genetics, physiology)
- Spleen
(cytology, immunology, pathology)
- T-Lymphocytes
(immunology)
- Time Factors
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