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 ~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 Gα-16 specifically bound (K(d) = 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 μM). 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 ≤ 1 μM). Thus, through an interaction with the C3aR, huC4a may elicit anaphylatoxic effects in guinea pigs but not in man.
|Zeitschrift||Journal of Immunology|
|Seiten (von - bis)||2089-2093|
|Publikationsstatus||Veröffentlicht - 01.09.1998|