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Extrahepatic complement biosynthesis: where, when and why?

The complement (C) system is a key component of innate immunity, playing a central role in defence against microorganisms and in the processing of immune complexes. It is also a powerful drive to inflammation and can, if unregulated, cause pathology. The last few years have seen a gradual realization that these events occur not only in the plasma, with its abundance of C proteins, but also in the tissues, where plasma C may penetrate poorly or not at all. The need for a functioning C system at these tissue sites must be met, either by increased influx of plasma C or by local synthesis. The purpose of this brief review is to summarize the evidence that C synthesis occurs at tissue sites and to advance the concept, suggested by studies in a variety of tissues, that local production of C is important in tissue homeostasis and immune defence.