Secretoneurin and chemoattractant receptor interactions.
Secretoneurin (SN) is a 33-amino acid peptide derived from secretogranin II (chromogranin C) which induces chemotaxis of monocytes but not neutrophils. In this study, we found that SN interacted with specific cell surface binding sites on human monocytes. The chemoattractants MCP-1, MCP-2 or fMLP could not compete for SN binding sites suggesting SN may bind to a novel chemotactic receptor. Additional studies showed that neither SN nor MCP-2 induced a rise in cytosolic Ca2+, and chemotaxis to SN was inhibited by cholera toxin (CT) and pertussis toxin (PT). Chemotactic desensitization studies demonstrated that fMLP, MCP-1, SN, and MCP-2 could all desensitize monocytes to subsequent SN stimulation. Our results indicate that SN binds to a cell surface receptor expressed on monocytes and activates signaling pathways which are sensitive to CT and PT.
Laboratory of Molecular Inflammation and Immunology, Robarts Research Institute, London, Ontario, Canada.
C
C
Kong
B M
BM
Gill
R
R
Rahimpour
L
L
Xu
R D
RD
Feldman
Q
Q
Xiao
T J
TJ
McDonald
L
L
Taupenot
S K
SK
Mahata
B
B
Singh
D T
DT
O'Connor
D J
DJ
Kelvin
D001665:Binding Sites / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D054412:Chemokine CCL8; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D037342:Pertussis Toxin; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism*; D053381:Secretogranin II; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
C515453:CCL8 protein, human; D018932:Chemokine CCL2; D054412:Chemokine CCL8; D018945:Monocyte Chemoattractant Proteins; D009479:Neuropeptides; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D053381:Secretogranin II; D010566:Virulence Factors, Bordetella; C081159:secretoneurin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002772:Cholera Toxin; D037342:Pertussis Toxin; D002118:Calcium