Serum amyloid A is a chemotactic agonist at FPR2, a low-affinity N-formylpeptide receptor on mouse neutrophils.
Serum amyloid A (SAA) is an acute-phase plasma protein and the source of amyloid A, which accumulates in lesions of secondary amyloidosis. SAA can induce phagocyte migration in vitro and in vivo, and is a specific chemotactic agonist for the human low-affinity N-formylpeptide receptor FPRL1R, a G-protein-coupled receptor expressed on phagocytes. Here we show that FPR2, a mouse counterpart of FPRL1R, is also an SAA receptor. SAA selectively induced calcium flux and chemotaxis in mouse PMN, which express FPR2, as well as in HEK 293 cells expressing recombinant FPR2 but not in HEK 293 cells expressing FPR, a closely related high affinity N-formylpeptide receptor. Consistent with this, SAA activity on PMN from FPR+/+ and FPR-/- mice was indistinguishable. Moreover, the prototype N-formylpeptide fMLF desensitized SAA-induced calcium flux in a dose-dependent manner in both mouse neutrophils and HEK 293/FPR2 transfectants. Our results suggest that FPR2 specifically mediates mouse neutrophil migration in response to SAA.
Liang
T S
TS
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
Wang
J M
JM
Murphy
P M
PM
Gao
J L
JL
D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000819:agonists*; D018000:Receptors, Peptide / Q000819:agonists*; D000685:Serum Amyloid A Protein / Q000378:metabolism* / Q000494:pharmacology
D001053:Apolipoproteins; D002630:Chemotactic Factors; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D000685:Serum Amyloid A Protein