Complement: more than a 'guard' against invading pathogens?

Recent studies have indicated that complement proteins might exert novel functions that are distinct from their well-established inflammatory role, by modulating cellular responses and cell-cell interactions that are crucial to early development and cell differentiation. Accumulating evidence suggests that complement might have important roles in diverse biologic processes, ranging from early hematopoiesis to skeletal and vascular development and normal reproduction. Furthermore, it is now becoming evident that complement-regulated pathways interact with other signaling networks and influence the outcome of complex developmental programs, such as limb regeneration in lower vertebrates and organ regeneration in mammals. These findings highlight a previously under-appreciated role of complement and might have important implications in the context of normal development by helping to elucidate the rather obscure role of innate immunity in such cell modulatory pathways.