Up‐regulation of platelet‐derived growth factor by peripheral‐blood leukocytes during experimental allergic encephalomyelitis

Abstract

In multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE), clinical disease is associated with infiltration of the central nervous system (CNS) by immune cells. Subsequent remission with remyelination has been linked to an increased occurrence of oligodendrocyte progenitor (O2A) cells. Platelet-derived growth factor (PDGF) and fibroblast growth factor-2 (FGF-2) are key growth factors for O2A cells, yet little is known about their relevance in EAE and MS. We analyzed the expression of PDGF, FGF-2, and their receptors by peripheral-blood leukocytes (PBLs) and lymphocyte subsets during MBP-induced EAE. Strong up-regulation of PDGF, but not FGF-2, was observed in PBLs, with the highest expression after the disease maximum. T, NK, and NKT cells expressed PDGF, which is a novel observation because thus far only monocytes/macrophages have been reported to express PDGF. These results extend the idea that growth factors may contribute to improved CNS tissue repair, including PDGF, which is secreted by lesion-homing immune cells. The production of PDGF by lymphocytes may have potential therapeutic value when activating or modulating T-cell responses in demyelinating diseases.

Synaptic Plasticity and PDGF Signaling Defects Underlie Clinical Progression in Multiple Sclerosis

“…PDGF, indeed, promotes neuronal differentiation (Williams et al, 1997;Erlandsson et al, 2001), improves significantly remyelination and oligodendrocyte density during acute demyelination, and reduces apoptosis during the recovery period after chronic demyelination (Vana et al, 2007). Furthermore, strong upregulation of PDGF occurs in peripheral lymphocytes of experimental MS, with the highest expression after the disease maximum (Koehler et al, 2008). PDGF has also been implicated in neuroprotection against energy deprivation and oxidative injury (Cheng and Mattson, 1995), against human immunodeficiency virus protein toxicity (Peng et al, 2008), and after injurious events, such as focal brain ischemia (Egawa-Tsuzuki et al, 2004).…”

How factors secreted from astrocytes impact myelin repair

“…Intrathecal administration of a viral vector expressing FGF-2 has been reported to suppress the clinical signs of experimental autoimmune encephalomyelitis (EAE), an animal model of MS (Ruffini et al, 2001). Another study examining PDGF expression in an EAE model reported that FGF-2 expression was limited to the CNS, but no changes in either its expression or its receptors were observed in peripheral blood leukocytes (Koehler et al, 2008). However, virally driven FGF-2 expression in the previous study demonstrated that increases in FGF-2 outside the CNS could attenuate the autoreactive T-cell response required for EAE (Ruffini et al, 2001).…”

G protein-coupled receptors as therapeutic targets for multiple sclerosis

“…PAF was upregulated in peripheral-blood leukocytes during EAE induction, and the receptor antagonist treatment or gene knockout led to alleviation of clinical signs [195,196,199,200]. Polymorphism of PAFR gene has also been identified to be correlated with the susceptibility to MS in human [201].…”