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An anaphylatoxin is a small signaling peptide released from a complement system component during activation. C3a and C5a are important examples: fragments derived from larger circulating proteins act as ligands for cell-surface receptors, connecting complement system activation with cellular responses involved in inflammation.^[ref]

The historical name is best understood through measurements of activity. Viktor A. Bokisch and colleagues isolated C3a and measured its ability to contract smooth muscle. Its activity could be inhibited or lost without simply equating every Complement C3 fragment with the same effect. This supplies a concrete example of a protein cleavage product acquiring a signaling role distinguishable from the remainder of its precursor.^[ref]

An anaphylatoxin is therefore a host-derived signal, rather than necessarily an externally introduced poison. A response to a fragment must be specified by the receptor, responding cell and experimental readout.

C3a is a small protein fragment released when Complement C3 is cleaved during activation of the complement system. It is an anaphylatoxin, associated with inflammatory responses, and is distinct from the larger C3b product involved in surface-associated complement reactions. Proteolysis can thus produce different activities from different parts of one precursor.^[ref]

In 1969, Viktor A. Bokisch and collaborators isolated C3a by several methods and tested its smooth muscle-contracting activity. Antiserum directed against C3a inhibited the biological response, connecting the isolated fragment to the activity rather than identifying it solely by a separation band. Further enzyme treatment changed its measured activities, showing why the amount of a fragment and its retained function are separate questions.^[ref]

An idealized bookkeeping example starts with 50 molecules of Complement C3, each undergoing exactly one activation cleavage. It produces 50 C3a fragments and 50 C3b fragments: 100 product molecules, but no doubling of total protein material. In an actual sample, production, further processing and removal all affect the measured concentration of C3a.

C5a is a small peptide fragment derived from complement C5 and classified as an anaphylatoxin. It can act as a signaling ligand; the name identifies a processed product rather than the whole circulating precursor. The originating pharmacology record identifies human C5a as an endogenous ligand associated with inflammatory signaling.^[ref]

Historical experiments tied fragment isolation to biological activity. In 1968, researchers separated larger and smaller fractions from guinea pig complement C5. The smaller fraction attracted rabbit polymorphonuclear leukocytes and showed activity in a guinea pig ileum assay. Those observations concern specific assay systems, not a human clinical experiment.^[ref]

For an original interpretation example, suppose equal amounts of two preparations are compared in both a chemotaxis assay and a smooth muscle response assay. Similar movement of leukocytes would not by itself establish equal smooth-muscle effects: the two readouts measure different responses. Conversely, detecting a fragment by an antibody does not guarantee that it retains either biological activity.

This separation of identity, amount and function is essential when discussing C5a. An anaphylatoxin classification names a biological activity; it does not itself diagnose a clinical episode of anaphylaxis.

Viktor A. Bokisch is the first-listed author of a 1969 study isolating C3a, a small fragment of the complement system protein Complement C3. The researchers connected the separated fragment with smooth muscle contraction and showed that antibodies recognizing C3a could inhibit its biological activity. This joined chemical separation with a functional test.^[ref]

The experiment illustrates why identifying a protein fragment requires more than detecting a smaller molecule. Separating it, distinguishing it from C3b with antibodies, and testing its effect gave complementary evidence. The study also found that a serum preparation could inactivate the anaphylatoxin activity, showing that generation and removal of an active signal are separate parts of complement system regulation.^[ref]