Evolution of anaphylatoxins, their diversity and novel roles in innate immunity: Insights from the study of fish complement

Anaphylatoxins are small molecules (∼9 kDa) that are generated as a result of the activation of the complement system. These molecules play an important role in inflammation, and they are responsible for the activation of various innate and adaptive immune processes. The study of these important inflammatory molecules has been restricted to mammalian species so far. Recent studies have shown that teleost fish, unlike any other known animal species, contain multiple forms of the C3a anaphylatoxin, all of which are functionally active and play a prominent role in inducing superoxide production in fish leukocytes. The C5a anaphylatoxin has also been characterized in these animals, and like in mammals, it plays an important role in leukocyte chemotaxis and in triggering the respiratory burst of leukocytes. Interestingly, it has been shown that rainbow trout anaphylatoxins play an unexpected role in enhancing phagocytosis of particles. C5a and C3a receptors have recently been cloned and characterized in rainbow trout, suggesting that the duplication of these receptors from a common ancestor occurred before the emergence of teleosts. The studies derived from these molecules in teleost fish indicate that the basic structure and function of anaphylatoxins and their receptors, have been conserved for more than 300 million years.