title: Human anaphylatoxin C4a is a potent agonist of the guinea pig but not the human C3a receptor.
abstract: The interaction of human anaphylatoxin C4a with the guinea pig (gp) and human (hu) C3a receptors (C3aR) was analyzed using human rC4a, which exhibited C4a-specific activity on guinea pig platelets. A gpC3aR of 475 residues with a large second extracellular loop and a peptide sequence approximately 60% identical to the huC3aR was isolated from a genomic DNA library and found to be expressed in guinea pig heart, lung, and spleen. HEK-293 cells cotransfected with this clone, and a cDNA encoding G alpha-16 specifically bound (Kd = 1.6+/-0.7 nM) and responded functionally to C3a with an intracellular calcium mobilization (ED50 = 0.18+/-0.02 nM). Human rC4a weakly bound to both the hu- and gpC3aR (IC50 > 1 microM). However, only HEK-293 cells expressing the gpC3aR responded functionally to rC4a (ED50 = 8.7+/-0.52 nM), while cells expressing the huC3aR did not (c < or = 1 microM). Thus, through an interaction with the C3aR, huC4a may elicit anaphylatoxic effects in guinea pigs but not in man.
authors.affiliation: Institute of Medical Microbiology, Hannover Medical School, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Lienenklaus
authors.forename: R S
authors.initials: RS
authors.lastname: Ames
authors.forename: M A
authors.initials: MA
authors.lastname: Tornetta
authors.forename: H M
authors.initials: HM
authors.lastname: Sarau
authors.forename: J J
authors.initials: JJ
authors.lastname: Foley
authors.forename: T
authors.initials: T
authors.lastname: Crass
authors.forename: B
authors.initials: B
authors.lastname: Sohns
authors.forename: U
authors.initials: U
authors.lastname: Raffetseder
authors.forename: M
authors.initials: M
authors.lastname: Grove
authors.forename: A
authors.initials: A
authors.lastname: Hölzer
authors.forename: A
authors.initials: A
authors.lastname: Klos
authors.forename: J
authors.initials: J
authors.lastname: Köhl
authors.forename: W
authors.initials: W
authors.lastname: Bautsch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D015934:Complement C4a / Q000819:agonists* / Q000235:genetics; D006168:Guinea Pigs; D006801:Humans; D007668:Kidney; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D015539:Platelet Activation / Q000187:drug effects / Q000276:immunology; D011951:Receptors, Complement / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D008565:Membrane Proteins; D011951:Receptors, Complement; D011994:Recombinant Proteins; C085567:complement C3a receptor; D015934:Complement C4a