title: Interleukin-1 upregulates anaphylatoxin receptors on mononuclear cells.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massschusetts 02114, USA.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Takabayashi
authors.forename: Soichi
authors.initials: S
authors.lastname: Shimizu
authors.forename: Burton D
authors.initials: BD
authors.lastname: Clark
authors.forename: Martin
authors.initials: M
authors.lastname: Beinborn
authors.forename: John F
authors.initials: JF
authors.lastname: Burke
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Gelfand
mesh_terms: D000706:Anaphylatoxins / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D015926:Complement C3a / Q000378:metabolism / Q000494:pharmacology; D015936:Complement C5a / Q000378:metabolism / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D037342:Pertussis Toxin / Q000494:pharmacology; D044087:Receptor, Anaphylatoxin C5a / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000706:Anaphylatoxins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016177:Macrophage-1 Antigen; D044087:Receptor, Anaphylatoxin C5a; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D015926:Complement C3a; D015936:Complement C5a; D037342:Pertussis Toxin; D002118:Calcium