Novel chemoattractant peptides for human leukocytes.
Phospholipase A(2) plays a key role in phagocytic cell functions. By screening a synthetic hexapeptide combinatorial library, we identified 24 novel peptides based on their ability to stimulate arachidonic acid release associated with cytosolic phospholipase A(2) activity in differentiated HL60 cells. The identified peptides, that contain the consensus sequence (K/R/M)KYY(P/V/Y)M, also induce intracellular calcium release in a pertussis toxin-sensitive manner showing specific action on phagocytic leukocytes, but not on other cells. Functionally, the peptides stimulate superoxide generation and chemotactic migration in human neutrophils and monocytes. Four of the tested active peptides were ligands for formyl peptide receptor like 1. Among these, two peptides with the consensus sequence (R/M)KYYYM can induce intracellular calcium release in undifferentiated HL60 cells that do not express formyl peptide receptor like 1, indicating usage of other receptor(s). A study of intracellular signaling in differentiated HL60 cells induced by the peptides has revealed that four of the novel peptides can induce extracellular signal-regulated protein kinase activation via shared and distinct signaling pathways, based on their dependence of phospatidylinositol-3-kinase, protein kinase C, and MEK. These peptides provide previously unavailable tools for study of differential signaling in leukocytes.
Bae
Yoe-Sik
YS
Department of Biochemistry, College of Medicine, Medical Research Center for Cancer Molecular Therapy, Dong-A University, Busan 02-714, South Korea.
Park
Eun-Young
EY
Kim
Youndong
Y
He
Rong
R
Ye
Richard D
RD
Kwak
Jong-Young
JY
Suh
Pann-Ghill
PG
Ryu
Sung Ho
SH
D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D010741:Phospholipases A / Q000502:physiology*; D044042:Receptors, Formyl Peptide / Q000378:metabolism; D044067:Receptors, Lipoxin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
D002630:Chemotactic Factors; C105101:FPR2 protein, human; D010455:Peptides; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D013481:Superoxides; D016718:Arachidonic Acid; D010741:Phospholipases A; D002118:Calcium