Leukemia Inhibitory Factor Is an Autocrine Survival Factor for Schwann Cells

Abstract

Schwann cells play a major role in promoting nerve survival and regeneration after injury. Their activities include providing neurotrophic factors and increasing the production of extracellular matrix components and cell surface adhesion molecules to promote axon regeneration. Following nerve transection, leukemia inhibitory factor (LIF) is up-regulated by Schwann cells at the injury site. LIF receptors are also up-regulated at the nerve injury site, but their cellular localization and function have not been fully characterized. We demonstrate that Schwann cells express mRNAs for LIF and the LIF receptor components LIF receptor subunit beta and glycoprotein 130 in vitro. We also show that although LIF is not required for the genesis of Schwann cells, it can potentiate the survival of differentiated Schwann cells in the context of neuregulin support. Not only does exogenous LIF promote survival under these conditions, but addition of the soluble LIF receptor (LIF binding protein) and anti-LIF antibodies significantly reduced cell survival, suggesting that LIF exerts autocrine effects. These results suggest that Schwann cell survival following nerve injury is potentially modulated by LIF.

Schwann cell proliferation during Wallerian degeneration is not necessary for regeneration and remyelination of the peripheral nerves: Axon-dependent removal of newly generated Schwann cells by apoptosis

“…Unlike Schwann cell precursors (S100 − ), S100 + Schwann cells survive in culture in the absence of axonal contact owing to the autocrine loop (Cheng et al 1998;Dowsing et al 1999;Meier et al 1999). However, our data indicates that the S100 + cells found in adult PNS following nerve injury are susceptible to death in the absence of axonal contact.…”

Triple Knock-Out ofCNTF,LIF, andCT-1Defines Cooperative and Distinct Roles of these Neurotrophic Factors for Motoneuron Maintenance and Function

“…However, only very low levels of LIF mRNA are expressed in intact postnatal nerves, but a rapid and dramatic increase occurs when nerves are lesioned (Banner and Patterson, 1994;Curtis et al, 1994;Sun et al, 1996). LIF acts as an autocrine survival factor for Schwann cells (Dowsing et al, 1999) and may play a role as a regulator of macrophage attraction to the lesioned nerve (Tofaris et al, 2002). Third, LIF can be released from Schwann cells via the classical secretory pathway, in contrast to the CNTF protein, which lacks a conventional leader sequence.…”

Chronic nerve compression induces concurrent apoptosis and proliferation of Schwann cells

“…What this signal is remains to be determined. During early development, Schwann cell apoptosis is regulated by autocrine signaling from molecules such as insulin-like growth factor, leukemia inhibitory factor, and neurotrophin-3 (Dowsing et al, 1999;Meier et al, 1999;Syroid et al, 1999), and these signaling molecules may play some role following nerve compression. With the creation of P0-hGH transgenic mice, Messing et al (1992) provided one of the earlier reports supporting the idea that Schwann cell proliferation and apoptosis may be coupled.…”