Axons in the peripheral nervous system (PNS) regenerate after transection injury and from functional connections with muscle and with sensory receptor organs. This regenerative capacity is not present in the central nervous system although the same neuronal cell body in the case of the dorsal root ganglion (DRG), may give rise to both peripheral and central axons. It has been demonstrated that in response to injury, non-neuronal cells in the distal peripheral nerve produce a soluble factor which enhances survival of and neurite outgrowth from DRG neurons in vitro. The activity is not due to NGF and the time course of induction suggest it may be important in determining the success of regeneration. Although many putative nervous system trophic factors have been identified, this is the first that is temporally limited to a specific biological event, namely nerve injury. It is proposed to isolated this factor using non-denaturing preparative column chromatography. The polyacrylamide-agarose gel system will partially separate proteins on the basis of molecular size. Monoclonal antibodies will be generated against fractions from the chromatographic separation and used to isolate the factor by solid phase immuno-affinity methods. Specific activity will be monitored using separate bioassays for neruon survival and neurite outgrowth. In parallel with the isolation, the biological activity will be characterized in terms of specificity for target neurons of the PNS, role of non-neuronal cells, and identification of cell type producing the activity. When antibodies can be prepared against the factor, their effect in development and regeneration will be observed. In the future, studies will determine whether this activity is present in human nerve and whether it is altered in specific disease states of man or in animal models.
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