A synthetic peptide (P-21) derived from asp-hemolysin inhibits the induction of macrophage proliferation by oxidized low-density lipoprotein.
Macrophage-derived foam cells play an important role in atherosclerotic lesions. Oxidized low-density lipoprotein (OxLDL) induces macrophage proliferation via the specific uptake of lysophosphatidylcholine (LysoPC) of OxLDL by class A, type I and type II macrophage scavenger receptors. We have previously shown that Asp-hemolysin from Aspergillus fumigatus binds to LysoPC as a typical lipid moiety of OxLDL. This study investigated the effect of the Asp-hemolysin-related peptide (P-21), a synthetic peptide derived from a region of Asp-hemolysin that is rich in positive charges, on macrophage proliferation induced by OxLDL. Mouse peritoneal macrophages were used for proliferation study. OxLDL induced macrophage proliferation in an oxidation time-dependent manner, and P-21 inhibited OxLDL-induced macrophage proliferation in a dose-dependent manner. Furthermore, the binding analysis of P-21 to OxLDL by dissociation-enhanced lanthanide fluorometric immunoassay indicated that P-21 binds to OxLDL. These results indicate that P-21 inhibits the OxLDL-induced macrophage proliferation through binding of P-21 to OxLDL.
Kumagai
Takeshi
T
First Department of Hygienic Chemistry, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi 981-8558, Japan. ta-kuma@tohoku-pharm.ac.jp
Ogawa
Norihiro
N
Tsutsumi
Hiromu
H
Ebina
Keiichi
K
Yokota
Katsushi
K
D000595:Amino Acid Sequence; D002455:Cell Division / Q000187:drug effects*; D005656:Fungal Proteins / Q000737:chemistry*; D006460:Hemolysin Proteins; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*
C089497:Asp-HS protein, Aspergillus fumigatus; D005656:Fungal Proteins; D006460:Hemolysin Proteins; D008077:Lipoproteins, LDL; D010455:Peptides; C099252:oxidized low density lipoprotein