Neuron Glia Biology

Research Article

Mast cells can contribute to axon–glial dissociation and fibrosis in peripheral nerve

Kelly R. Monka1a2, Jianqiang Wua1, Jon P. Williamsa1, Brenda A. Finneya1, Maureen E. Fitzgeralda1, Marie-Dominique Filippia1 and Nancy Ratnera1 c1

a1 Department of Pediatrics, Division of Experimental Hematology and Cancer Biology, 3333 Burnet Avenue, Cincinnati Children's Hospital Medical Center, Cincinnati, USA

a2 Present address, Department of Developmental Biology, Stanford University School of Medicine, Stanford, USA

Abstract

Expression of the human epidermal growth factor receptor (EGFR) in murine Schwann cells results in loss of axon–Schwann cell interactions and collagen deposition, modeling peripheral nerve response to injury and tumorigenesis. Mast cells infiltrate nerves in all three situations. We show that mast cells are present in normal mouse peripheral nerve beginning at 4 weeks of age, and that the number of mast-cells in EGFR+ nerves increases abruptly at 5–6 weeks of age as axons and Schwann cells dissociate. The increase in mast cell number is preceded and accompanied by elevated levels of mRNAs encoding the mast-cell chemoattractants Rantes, SCF and VEGF. Genetic ablation of mast cells and bone marrow reconstitution in W41 × EGFR+ mice indicate a role for mast cells in loss of axon−Schwann cell interactions and collagen deposition. Pharmacological stabilization of mast cells by disodium cromoglycate administration to EGFR+ mice also diminished loss of axon−Schwann cell interaction. Together these three lines of evidence support the hypothesis that mast cells can contribute to alterations in peripheral nerves.

(Received November 12 2007)

(Revised December 17 2007)

(Accepted January 11 2008)

Correspondence:

c1 Correspondence should be addressed to Nancy Ratner, Department of Pediatrics, Division of Experimental Hematology, 3333 Burnet Avenue, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA phone: +1 513 636 9469 fax: +1 513 636 3549 email: Nancy.Ratner@cchmc.org