Identification of C3a and N-truncated C3a as vascular permeability-enhancing factors from the exudate of chronic phase of carrageenan-induced inflammation in rats.

Two basic proteins enhancing vascular permeability have been purified from the exudate of the chronic phase of carrageenan-induced inflammation in rats. One major and one minor peak on reversed-phase HPLC showed molecular masses of 9.3 kDa and 7.6 kDa, respectively, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. NH2-terminal amino acid sequencing analysis of the purified proteins revealed that the major peak is identical to C3a, while the main sequence of the minor peak is identical to NH2-terminal 11 amino acids truncated C3a. In addition, plasmin was able to cleave C3a into the N-truncated C3a. Intradermal injection of both purified C3a and N-truncated C3a into rat skin enhanced vascular permeability, and the increased permeability was suppressed by the pretreatment with cyproheptadine. Our results suggest that the purified C3a and N-truncated C3a have the characteristics of anaphylatoxins and may contribute to exudation in the chronic phase of carrageenan-induced inflammation in rats.