Induction of macrophage migration through lactose-insensitive receptor by elastin-derived nonapeptides and their analog.
Elastin, one of the extracellular matrix components, is present in tissues requiring extensibility and resilience such as the aorta, lungs, ligaments and skin. Degradation of elastin is observed in diseases such as atherosclerosis, emphysema and metastasis. It has been suggested that degraded elastin-derived peptides interact with a variety of cell types and are involved in development of diseases. Two nonapeptides, Ala-Gly-Val-Pro-Gly-Leu-Gly-Val-Gly (AGVPGFGVG) and Ala-Gly-Val-Pro-Gly-Phe-Gly-Val-Gly (AGVPGFGVG), exist in hydrophobic regions of elastin. In this paper, we characterized these elastin-derived nonapeptides by macrophage migration assay. Both nonapeptides induced a maximal migration at 10(-8) M and elicited the same degree of responsiveness. To investigate the role of the sixth residue of the nonapeptides, seven analog peptides in which Leu or Phe is substituted by Ile, Val, Ala, Gly, Pro, Lys or Glu were synthesized and their macrophage migration activity tested. Among the nonapeptide analogs, only Ala-Gly-Val-Pro-Gly-Ile-Gly-Val-Gly induced the migration of macrophages at the optimal concentration of 10(-9) M and its responsiveness was the same as that of parent nonapeptide AGVPGFGVG. Results of the deactivation tests and the effect of lactose on macrophage migration showed that a lactose-insensitive receptor which mainly recognizes Ala-Gly-Val-Pro-Gly-Ile-Gly-Val-Gly is presumably present on the membrane of macrophages in addition to the elastin-binding protein (EBP) sensitive to lactose. These results suggest that Leu, Phe and Ile residues at the sixth position of elastin-derived nonapeptides are crucial for inducing macrophage migration and in particular, Ile residue is important for the recognition by receptor insensitive to lactose.
Maeda
Iori
I
Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, Iizuka, Fukuoka 820-8502, Japan. iori@bio.kyutech.ac.jp
Mizoiri
Noriaki
N
Briones
Maria Portia P
MP
Okamoto
Kouji
K
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004549:Elastin / Q000737:chemistry* / Q000494:pharmacology; D007785:Lactose / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D008297:Male; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism
D010455:Peptides; D011956:Receptors, Cell Surface; C054901:elastin-binding proteins; D004549:Elastin; D007785:Lactose