F2L, a peptide derived from heme-binding protein, inhibits formyl peptide receptor-mediated signaling.
F2L is an acetylated amino-terminal peptide derived from the cleavage of the human heme-binding protein. Very recently, F2L was identified as an endogenous chemoattractant peptide acting specifically through formyl peptide receptor-like (FPRL)2. In the present study, we report that F2L stimulates chemotactic migration in human neutrophils. However, F2L inhibits formyl peptide receptor (FPR) and FPRL1 activities, resulting in the complete inhibition of intracellular calcium increases, and superoxide generation induced by N-formyl-Met-Leu-Phe, MMK-1, or Trp-Lys-Tyr-Met-Val-d-Met (WKYMVm) in human neutrophils. In terms of the inhibitory role of F2L on FPR- and FPRL-mediated signaling, we found that F2L competitively inhibits the binding of (125)I-WKYMVm to its specific receptors, FPR and FPRL1. F2L is the first endogenous molecule that inhibits FPR- and FPRL1-mediated signaling, and is expected to be useful in the study of FPR and FPRL1 signaling and in the development of drugs to treat diseases involving the FPR family of receptors.
Lee
Ha Young
HY
Department of Biochemistry, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
Lee
Sun Young
SY
Shin
Eun Ha
EH
Kim
Sang Doo
SD
Kim
Jung Mo
JM
Lee
Mi-Sook
MS
Ryu
Sung Ho
SH
Bae
Yoe-Sik
YS
D002352:Carrier Proteins / Q000008:administration & dosage; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000008:administration & dosage*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D000081062:Heme-Binding Proteins; D006420:Hemeproteins / Q000008:administration & dosage; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000008:administration & dosage*; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D044067:Receptors, Lipoxin / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D002352:Carrier Proteins; D002630:Chemotactic Factors; C498127:F2L peptide, human; C105101:FPR2 protein, human; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D010455:Peptides; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin