CONICET | Buscador de Institutos y Recursos Humanos

Prostaglandins: their role in bone marrow mononuclear cell migration to the injured nerve. Vanina Usach1, Cecilia Casali2, Lucía Lavalle1, María del Carmen Fernández-Tomé2 y Patricia Setton-Avruj1. 1Cátedra de Química Biológica Patológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, IQUIFIB- Instituto Dr Alejandro Paladini, UBA-CONICET, Buenos Aires, Argentina. 2Cátedra de Biología Celular y Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, IQUIFIB- Instituto Dr Alejandro Paladini, UBA-CONICET, Buenos Aires, Argentina. We have previously described the reorganization of major myelin proteins MBP and P0 and axonal protein PGP 9.5 during sciatic nerve demyelination, as well as the migration of bone marrow mononuclear cells (BMMC) exclusively to the injured nerve. Once in the ipsilateral nerve, some BMMC colocalize with Schwann cell and nerve fiber markers. These cells accelerate the degeneration process and, as a consequence, promote the onset of regeneration. In this context, the aim of the present work was to evaluate the signals that could stimulate the recruitment of BMMC to the demyelinated nerve. To that end, adult rats were submitted to sciatic nerve crush to promote demyelination and confocal microscopy was used to determine whether the inhibition of prostaglandin (PG) synthesis with indomethacin affects the migration of transplanted BMMC. In the light of results obtained, we also evaluated the expression of ciclooxigenases (Cox), the key enzymes in PG biosynthesis. Our findings show that, as soon as 24 h post injury, BMMC arrived at the edges of the ipsilateral nerve and, after 3 days, they became part of the nerve. The treatment with indomethacin inhibited the migration of BMMC, suggesting that PG are somehow involved in the recruitment and migration of these cells. In support of these results, Cox-2 expression was induced 2 hours after nerve injury and was still upregulated 24 hours after nerve injury. Further experiments will be necessary to elucidate other possible biological signals involved in BMMC migration during the degeneration-regeneration process.

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