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The Journal of Neuroscience, September 1, 1998, 18(17):6713-6722

Complement Depletion Reduces Macrophage Infiltration and Activation during Wallerian Degeneration and Axonal Regeneration

Andrew T. Dailey^{1, 4}, Anthony M. Avellino¹, Lambertus Benthem², Jerry Silver³, and Michel Kliot¹

¹ Department of Neurological Surgery, University of Washington, Seattle, Washington 98195, ² Department of Medicine, Division of Endocrinology and Metabolism, Puget Sound Veterans Affairs Health Care Center, Seattle, Washington 98108, ³ Department of Neuroscience, Case Western Reserve University, Cleveland, Ohio 44106, and ⁴ Department of Neurosurgery, University of Utah, Salt Lake City, Utah 84132

After peripheral nerve injury, macrophages infiltrate the degenerating nerve and participate in the removal of myelin and axonal debris, in Schwann cell proliferation, and in axonal regeneration. In vitro studies have demonstrated the role serum complement plays in both macrophage invasion and activation during Wallerian degeneration of peripheral nerve. To determine its role in vivo, we depleted serum complement for 1 week in adult Lewis rats, using intravenously administered cobra venom factor. At 1 d after complement depletion the right sciatic nerve was crushed, and the animals were sacrificed 4 and 7 d later. Macrophage identification with ED-1 and CD11a monoclonal antibodies revealed a significant reduction in their recruitment into distal degenerating nerve in complement-depleted animals. Complement depletion also decreased macrophage activation, as indicated by their failure to become large and multivacuolated and their reduced capacity to clear myelin, which was evident at both light and electron microscopic levels. Axonal regeneration was delayed in complement-depleted animals. These findings support a role for serum complement in both the recruitment and activation of macrophages during peripheral nerve degeneration as well as a role for macrophages in promoting axonal regeneration.

Key words: complement; macrophage; peripheral nerve; Wallerian degeneration; regeneration; axon

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18176713-10$05.00/0

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