CCL11 (Eotaxin) induces CCR3-dependent smooth muscle cell migration.
OBJECTIVE
CCL11 (Eotaxin) is a potent eosinophil chemoattractant that is abundant in atheromatous plaques. The major receptor for CCL11 is CCR3, which is found on leukocytes and on some nonleukocytic cells. We sought to determine whether vascular smooth muscle cells (SMCs) possessed functional CCR3.


RESULTS
CCR3 mRNA (by RT-PCR) and protein (by Western blot analysis and flow cytometry) were present in mouse aortic SMCs. CCL11 induced concentration-dependent SMC chemotaxis in a modified Boyden chamber, with maximum effect seen at 100 ng/mL. SMC migration was markedly inhibited by antibody to CCR3, but not to CCR2. CCL11 also induced CCR3-dependent SMC migration in a scrape-wound assay. CCL11 had no effect on SMC proliferation. CCR3 and CCL11 staining were minimal in the normal arterial wall, but were abundant in medial SMC and intimal SMC 5 days and 28 days after mouse femoral arterial injury, respectively, times at which SMCs possess a more migratory phenotype.


CONCLUSIONS
These data demonstrate that SMCs possess CCR3 under conditions associated with migration and that CCL11 is a potent chemotactic factor for SMCs. Because CCL11 is expressed abundantly in SMC-rich areas of the atherosclerotic plaque and in injured arteries, it may play an important role in regulating SMC migration.
Kodali
Ravindra B
RB
Zena and Michael A. Wiener Cardiovascular Institute and Department of Medicine, The Mount Sinai School of Medicine, New York, NY, USA.
Kim
William J H
WJ
Galaria
Irfan I
II
Miller
Christine
C
Schecter
Alison D
AD
Lira
Sergio A
SA
Taubman
Mark B
MB
D000818:Animals; D001011:Aorta / Q000166:cytology; D000077214:Becaplermin; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000502:physiology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000494:pharmacology* / Q000502:physiology; D002630:Chemotactic Factors / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects*; D004804:Eosinophils / Q000737:chemistry; D005263:Femoral Artery / Q000293:injuries / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000096:biosynthesis; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
C515456:CCL11 protein, human; C515350:CCR3 protein, human; C515457:Ccl11 protein, mouse; C515351:Ccr3 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002630:Chemotactic Factors; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D000077214:Becaplermin