Monokine generation as a consequence of binding of human C5a anaphylatoxin to specific cell-surface receptors

The addition of human C5a to antigen-stimulated cultures results in dose-dependent augmentation of the primary antibody response to antigen. The specificity of this effect is confirmed by the ability of C5ades Arg, but not of the structurally analogous C3a anaphylatoxin, to act in a parallel fashion. This effect appears to be mediated by interaction of C5a with cells of the monocytoid/macrophage lineage. These cells have been shown to bear surface receptors specific for C5a. In order to examine the role of soluble mediators in these events, culture supernatants were generated from splenic adherent cells or macrophage cell lines after exposure to a brief pulse of human C5a. Supernatants from the macrophage-like cell line P388D1, which bears surface receptors for C5a, enhance the PFC response to antigen, whereas those from the closely related cell line P388, which lacks surface receptors for C5a, fail to cause enhancement. Supernatants from splenic adherent cells, which also bear C5a receptors, similarly augment the SRBC response. Active supernatants, but not those devoid of activity, contain IL-1 activity. None of the supernatants contain IL-2 activity. These observations suggest that the recently described role of human C5a as an immunopotentiating modulator is mediated by its ability to induce production of IL-1 upon binding to specific receptors at the macrophage cell surface.