Adhesion molecules involved in macrophage responses to wallerian degeneration in the murine peripheral nervous system

Brown, H.C., Castaño, A., Fearn, S., Townsend, M., Edwards, G., Streuli, C. and Perry, V.H. (1997) Adhesion molecules involved in macrophage responses to wallerian degeneration in the murine peripheral nervous system. European Journal of Neuroscience, 9 (10), 2057-2063. (doi:10.1111/j.1460-9568.1997.tb01373.x).

Abstract

When a peripheral nerve is damaged the severed axon undergoes Wallerian degeneration. The distal nerve is infiltrated by large numbers of monocyte-derived macrophages which participate in the phagocytosis of degenerating myelin. In other tissues, adhesion molecules play a crucial role in leukocyte recruitment during inflammation. Blood-borne cells enter damaged tissue by interacting with adhesion molecules expressed on activated endothelium. Having crossed the endothelium, leukocytes must adhere and migrate within the tissue. We investigated the adhesion molecules involved in both stages of the macrophage response to transection of one sciatic nerve of BALB/c mice. By injecting monoclonal antibodies in vivo, before and after peripheral nerve injury, we showed that intercellular adhesion molecule-1 (ICAM-1) and integrins α₄β1 (VLA-4) and α(M)β₂ (type 3 complement receptor) are unlikely to be involved in the transendothelial migration of monocytes responding to peripheral nerve degeneration. We also studied the adhesion of macrophages within the endoneurium, using an in vitro adhesion assay. Macrophages showed much greater levels of adhesion to cryostat sections of transected nerves than to control nerves. This increased adhesion was partially inhibited by antibodies to the β1-integrin chain, and more strongly inhibited by the extracellular matrix molecules fibronectin and collagen. Adhesion was unaffected by laminin-1 and by antibodies to other adhesion molecules, including α₄β_1- and α₅β₁-integrins. Thus we conclude that monocyte entry into a degenerating peripheral nerve is independent of α(L)β₂/α(M)β₂-ICAM-1 or α₄β₁/VCAM-1 interactions, and that adhesion within the endoneurium is mediated in part by a β1-integrin other than α₄β₁ or α₅β₁.

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