Activation of human neutrophils by a synthetic anti-microbial peptide, KLKLLLLLKLK-NH2, via cell surface calreticulin.
We previously reported that a synthetic anti-bacterial peptide, KLKLLLLLKLK-NH2 (L5), showed significant chemotherapeutic activity in methicillin-resistant Staphylococcus aureus-infected mice, and its ability to activate human neutrophils was related to its chemotherapeutic activity. In this study, we found that activation of neutrophils by L5 was inhibited by pertussis toxin, suggesting that GTP-binding protein (G-protein) participates in this process. We isolated an L5-binding protein, which turned out to be human calreticulin, with a molecular mass of 60 kDa from neutrophil membranes. From experiments using an anti-calreticulin antibody, we proposed that calreticulin is partly localized on the surface of neutrophils, and L5-bound calreticulin transmits a signal into cells via G-protein to activate neutrophils to generate superoxide anion.
Cho
J H
JH
Nabori Special Laboratory, The Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
Homma
K
K
Kanegasaki
S
S
Natori
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D037282:Calreticulin; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D012261:Ribonucleoproteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism
D000890:Anti-Infective Agents; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D002352:Carrier Proteins; D008565:Membrane Proteins; D009842:Oligopeptides; D012261:Ribonucleoproteins; C096884:nysyl-leucyl-lysyl-leucyl-leucyl-leucyl-leucyl-leucyl-lysyl-leucyl-lysinamide; D013481:Superoxides