BACKGROUND: 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. METHODS: 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. RESULTS: Basal 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. CONCLUSION: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: Basal 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. CONCLUSION: 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.
Authors: Raymond J Langley; Neerad C Mishra; Juan Carlos Peña-Philippides; Brandon J Rice; Jean-Clare Seagrave; Shashi P Singh; Mohan L Sopori Journal: J Toxicol Environ Health A Date: 2011
Authors: Thomas Ruby; Catherine Whittaker; David R Withers; Mounira K Chelbi-Alix; Veronique Morin; Anne Oudin; John R Young; Rima Zoorob Journal: J Virol Date: 2006-09 Impact factor: 5.103
Authors: Anita Ignatius; Philipp Schoengraf; Ludwika Kreja; Astrid Liedert; Stefan Recknagel; Sebastian Kandert; Rolf E Brenner; Marion Schneider; John D Lambris; Markus Huber-Lang Journal: J Cell Biochem Date: 2011-09 Impact factor: 4.429
Authors: Eleazar Soto; Roberto Romero; Karina Richani; Jimmy Espinoza; Tinnakorn Chaiworapongsa; Jyh Kae Nien; Sam S Edwin; Yeon Mee Kim; Joon Seok Hong; Luis F Goncalves; Lami Yeo; Moshe Mazor; Sonia S Hassan; Juan Pedro Kusanovic Journal: J Matern Fetal Neonatal Med Date: 2010-07
Authors: Yaël Mamane; Chi Chung Chan; Genevieve Lavallee; Nicolas Morin; Li-Jing Xu; JingQi Huang; Robert Gordon; Winston Thomas; John Lamb; Eric E Schadt; Brian P Kennedy; Joseph A Mancini Journal: Diabetes Date: 2009-07-06 Impact factor: 9.461