Complement factors in adult peripheral nerve: a potential role in energy metabolism

Complement cascade factors are known to play a critical role in myelin clearance after peripheral nerve injury. Here we show that components of both the classical (C1qa, C1qb, C1qc, C2 and C4) and alternative (C3, B and adipsin) pathways are expressed by uninjured peripheral nerve as well. mRNAs of components of the alternative pathway were predominantly found in the peri/epineurium, although factor C3 and factor B were also detected in the endoneurial compartment of adult nerve. Interestingly, adipsin mRNA was detected only in peri/epineurium, while adipsin protein was present in both peri/epineurium and endoneurium. This suggests that adipsin is transported to the endoneurium via the circulation from the peri/epineurium or outside of the nerve. Factor 5 and factor 9, necessary for the formation of the membrane-attack complex, were not detected in any part of the healthy peripheral nerve, which together with the observed presence of negative regulators of complement activation, is likely to prevent damage to the healthy nerve caused by complement activation. By analogy with the known role of complement factors in fat, we propose that local expression of these factors plays a role in the regulation of fatty acid homeostasis in the nerve and, thereby, in energy metabolism cross-talk between different compartments of the peripheral nerve.