First Author | Lienenklaus S | Year | 1998 |
Journal | J Immunol | Volume | 161 |
Issue | 5 | Pages | 2089-93 |
PubMed ID | 9725198 | Mgi Jnum | J:49259 |
Mgi Id | MGI:1277048 | Doi | 10.4049/jimmunol.161.5.2089 |
Citation | Lienenklaus S, et al. (1998) Human anaphylatoxin C4a is a potent agonist of the guinea pig but not the human C3a receptor. J Immunol 161(5):2089-93 |
abstractText | 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. |