EXPRESSION OF JE (MONOCYTE CHEMOATTRACTANT PROTEIN-1) IS INDUCED BY SCIATIC AXOTOMY IN WILD-TYPE RODENTS BUT NOT IN C57BL WLD(S) MICE/

Recruitment of hematogenous myelomonocytic cells into injured peripher al nerve is essential for axonal regeneration. The monocyte chemoattra ctant protein-1 (JE) and melanoma growth stimulatory activity/gro (KC) ''immediate early'' gene products may be important in this process as these proteins are potent chemoattractants for macrophages and neutro phils, respectively. To test this hypothesis, we examined JE and KC ac tivation in rat sciatic nerve 0-30 days after surgical transection. RT -PCR and in situ hybridization analyses of JE and KC expression demons trates these mRNAs are present in injured nerve, first being expressed by a cellular subpopulation within the zone of trauma by 1.5 hours af ter injury. By 16 hours post-transection a subpopulation of JE-positiv e endoneurial cells is found in the proximal stump and throughout the distal nerve segment, with maximal mRNA accumulation occurring 1 day a fter injury and expression persisting to 18 days postaxotomy, a period preceding and coincident with macrophage infiltration. In contrast, b y 3 days postaxotomy KC expression is markedly diminished, consistent with the limited neutrophilic response to nerve injury. JE expression was also examined in C57BL/Wld(s) mice, which have delayed Wallerian d egeneration associated with a failure of macrophage recruitment, and t heir parental C57BL/6J strain. Although JE mRNA is inducible in sciati c nerve from C57BL/6J mice, these transcripts are undetectable in inju red nerve from C57BL/Wld(s) mice. Our findings suggest that activation of the JE locus is at least partially responsible for macrophage inva sion of injured peripheral nerve. Furthermore, defective postaxotomy m acrophage recruitment in C57BL/Wld(s) mice may involve a failure of JE induction.