The importance of pentraxin-3 on primary glial cell proliferation and ischemic preconditioning

S. Maysami, C. Smedley, C. Ugbode, N. Rothewell, E. Pinteaux

    Research output: Contribution to conferencePoster

    Abstract

    Pentraxin-3 (PTX3), an acute phase protein, is produced by activated monocytes, macrophages, dendritic, endothelial, and immune cells that are actively participate in the stroke pathology. Production of PTX3 is under stimulatory effect of inflammatory and proinflammatory molecules (ie. LPS, IL-1, & TNF). PTX3 specifically binds to apoptotic and necrotic cells to be removed from living tissues after insult. However, the exact role of PTX3 in brain pathologies (i.e. in ischemic preconditioning (IP) and tolerance (IT)) is not fully understood. IP is a transient ischemic stress that can ameliorate the extent of irreversible injury from the subsequent ischemia (the phenomenon of IT). Previously, we demonstrated that proliferating progenitor cells are a required cellular element for induction of IT (Maysami et al., 2008) and that cytokines and chemokines play an important role in cell proliferation (Maysami et al., 2006; Patel et al., 2010). Here we demonstrate for the first time the importance of PTX3 in induction of proliferation in primary glial cells and its potential role in induction of cell proliferation after IP.Using primary mixed glial culture of mouse origin we showed that preincubation of glial cells with PTX3 significantlyenhanced proliferation of these cells after 48 hours. This effect was 50% less than the one observed after applying the growth factor, FGF2. Co-application of FGF2 and PTX3 showed synergistic effect on cell proliferation on primary cells.PTX3 could differentially regulate cell proliferation at earlier time points. This delay in pentraxin-mediated cell proliferation suggested activation of intermediate signalling molecules. Western blot analysis showed significant increase in the expression level of ERK and pERK in the presence of PTX3 and/or FGF2 (as a positive control). The effect of PTX3 on glial cell proliferation was not via enhanced secretion of cytokines/chemokines (i.e. CXCL1). We also used a mouse model of transient ischemia and occluded the middle cerebral artery for 10-15 min. Histological analysis showed minimal to no infiltration of IgG in these brains. Further observations showed increased number ofBrdU positive proliferating progenitor cells. Interestingly, a significant increase in the expression of pentraxin-3 was observed at subventricular zone (48 and 72 hours) after IP. Hence, PTX3 can be one of the key molecules involved in cell proliferation after IP and may play a role in reduction of neurotoxicity observed in IT. Further experiments are in progress to reveal the exact cellular and molecular mechanismsinvolved in the PTX3-mediated cell proliferation and survival in vitro as well as in vivo.
    Original languageEnglish
    Publication statusPublished - 16 Nov 2011
    EventSociety For Neuroscience -
    Duration: 11 Nov 201116 Nov 2011

    Conference

    ConferenceSociety For Neuroscience
    Period11/11/1116/11/11

    Keywords

    • Progenitor cells
    • Proliferation
    • Ischemic Preconditioning
    • Pentraxin-3
    • ERK
    • pERK

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