• Tsukasa Takabayashi, Soichi Shimizu, Burton D Clark, Martin Beinborn, John F Burke, and Jeffrey A Gelfand.
• Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massschusetts 02114, USA.
• Surgery. 2004 May 1; 135 (5): 544-54.

BackgroundThe anaphylatoxins, C3a and C5a, that are generated during trauma, major surgery, or infection are potent proinflammatory mediators that increase interleukin (IL-1) cytokine synthesis. We investigated the effects of IL-1 on anaphylatoxin receptor expression in monocytes.MethodsA human monocytic cell line, MONO-MAC-6, was used. C3a and C5a binding sites were assayed by competitive binding. Levels of messenger RNA for the C3a and C5a receptors were analyzed by reverse transcriptase-polymerase chain reaction. Changes of free cytosolic Ca(2+) concentration ([Ca(2+)]i) in response to C3a and C5a were measured.ResultsBasal MONO-MAC-6 cell sites for C3a and C5a binding were 10900 C3aR/cell (K(d)=2.0 nmol/L), 8700 C5aR/cell (K(d)=0.9 nmol/L). IL-1alpha increased sites for both C3a (61% increase; P <.01) and C5a (71% increase; P <.001). Levels of C3aR and C5aR messenger RNA also increased in IL-1alpha-stimulated cells. Receptors were coupled to functional responses, which were demonstrated by C3a- or C5a-induced [Ca(2+)]i increases. IL-1 receptor antagonist blocked the effects of IL-1alpha upregulation of anaphylatoxin receptors.ConclusionThese results suggest that there is an additional link between IL-1 and anaphylatoxins to amplify proinflammatory effects through monocytes and macrophages. Although C3a and C5a can increase the monocyte production of IL-1, IL-1 increases monocyte expression of receptors for these anaphylatoxins, which further amplifies inflammation.

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