Anaphylatoxin-mediated contraction of guinea pig lung strips: a nonhistamine tissue response.

Contractile effects of purified porcine C3a and C5a anaphylatoxins on guinea pig pulmonary tissue were determined in vitro by using a peripheral airway preparation. A thin strip of lung is mounted in an organ bath at 37°C and attached to a transducer that records isotonic contractions. Both anaphylatoxins proved to be more potent than either histamine or acetylcholine on this tissue. Porcine C5a induces threshold contractions of pulmonary tissue at a concentration of 6 × 10−10 M, approaching a maximal effect at 6 × 10−7 M. A measurable effect is observed with C3a at 1 × 10−8 M, maximizing at 5 × 10−7 M. Histamine and acetylcholine seldom contract the tissue at a concentration below 10−7 M and induce maximal contraction only at concentrations in excess of 10−5 M. Therefore, the order of potency is C5a > C3a > histamine > acetylcholine for contraction of guinea pig lung strips. The relative magnitude of the contraction induced in guinea pig lung strips by these mediators is highly variable. Porcine C5a and histamine induce contractions 2 to 3 times greater than the maximal contraction induced by acetylcholine. In contrast, the maximal C3a-induced contraction is only 40 to 50% of the maximal acetylcholine-induced contractions. Consequently, the magnitude of the induced response follows the order C5a ≃ histamine > acetylcholine > C3a. As in other tissues, repeated application of either anaphylatoxin desensitizes the lung strips to that factor and the contractile responses are abrogated. However, cross-desensitization is not observed between C3a and C5a. Contractile responses to smooth muscle induced by the anaphylatoxins in certain tissues are known to be mediated by histamine and other vasoamines, particularly in the guinea pig ileum. Therefore, the C3a and C5a dose-response curves in pulmonary tissue were examined in the presence of H1 and H2 type antihistamines. These drugs had no apparent effect on anaphylatoxin-induced responses. The contractile response induced in guinea pig peripheral airways by the C3a and C5a anaphylatoxins is apparently independent of vasoamine release. From these studies, we conclude that the anaphylatoxins are functionally capable of mediating or potentiating complement-associated pulmonary injury without the involvement of histamine or other vasoactive amines.