Interleukin-1 upregulates anaphylatoxin receptors on mononuclear cells

• Published in: Surgery 2004-05, Vol.135 (5), p.544-554
• Main Authors: Takabayashi, Tsukasa, Shimizu, Soichi, Clark, Burton D, Beinborn, Martin, Burke, John F, Gelfand, Jeffrey A
• Format: Article
• Language: English
• Subjects: Anaphylatoxins - metabolism; Binding Sites - drug effects; Biological and medical sciences; Calcium - metabolism; Cell Line; Complement C3a - metabolism; Complement C3a - pharmacology; Complement C5a - metabolism; Complement C5a - pharmacology; Cytosol - metabolism; Dose-Response Relationship, Drug; Gene Expression - drug effects; General aspects; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1 - administration & dosage; Interleukin-1 - pharmacology; Interleukin-1 - physiology; Macrophage-1 Antigen - genetics; Macrophage-1 Antigen - metabolism; Medical sciences; Monocytes - drug effects; Monocytes - metabolism; Osmolar Concentration; Pertussis Toxin - pharmacology; Receptor, Anaphylatoxin C5a - genetics; Receptor, Anaphylatoxin C5a - metabolism; Receptors, Cell Surface - metabolism; Recombinant Proteins - pharmacology; Sialoglycoproteins - pharmacology; Up-Regulation - drug effects
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/j.surg.2003.09.010

The 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. A 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. Basal MONO-MAC-6 cell sites for C3a and C5a binding were 10,900 C3aR/cell (K d = 2.0 nmol/L), 8700 C5aR/cell (K d = 0.9 nmol/L). IL-1α 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-1α-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-1α upregulation of anaphylatoxin receptors. These 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.