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Induction of macrophage chemotaxis by aortic extracts of the mgR Marfan mouse model and a GxxPG-containing fibrillin-1 fragment.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Guo, Gao Booms, Patrick Halushka, Marc K. Dietz, Harry C. Ney, Andreas Stricker, Sigmar Hecht, Jochen Mundlos, Stefan Robinson, Peter N. |
| Copyright Year | 2006 |
| Abstract | BACKGROUND The primary cause of early death in untreated Marfan syndrome (MFS) patients is aortic dilatation and dissection. METHODS AND RESULTS We investigated whether ascending aortic samples from the fibrillin-1-underexpressing mgR mouse model for MFS or a recombinant fibrillin-1 fragment containing an elastin-binding protein (EBP) recognition sequence can act as chemotactic stimuli for macrophages. Both the aortic extracts from the mgR/mgR mice and the fibrillin-1 fragment significantly increased macrophage chemotaxis compared with extracts from wild-type mice or buffer controls. The chemotactic response was significantly diminished by pretreatment of macrophages with lactose or with the elastin-derived peptide VGVAPG and by pretreatment of samples with a monoclonal antibody directed against an EBP recognition sequence. Mutation of the EBP recognition sequence in the fibrillin-1 fragment also abolished the chemotactic response. These results indicate the involvement of EBP in mediating the effects. Additionally, investigation of macrophages in aortic specimens of MFS patients demonstrated macrophage infiltration in the tunica media. CONCLUSIONS Our findings demonstrate that aortic extracts from mgR/mgR mice can stimulate macrophage chemotaxis by interaction with EBP and show that a fibrillin-1 fragment possesses chemotactic stimulatory activity similar to that of elastin degradation peptides. They provide a plausible molecular mechanism for the inflammatory infiltrates observed in the mgR mouse model and suggest that inflammation may represent a component of the complex pathogenesis of MFS. |
| Starting Page | 79 |
| Ending Page | 91 |
| Page Count | 13 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://circ.ahajournals.org/content/circulationaha/114/17/1855.full.pdf?download=true |
| PubMed reference number | 17030689v1 |
| Volume Number | 114 |
| Issue Number | 17 |
| Journal | Circulation |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Animal Model Buffers Dilate procedure Fibrillins Infiltration Lactose Marfan Syndrome Monoclonal Antibodies Patients Recombinants Specimen Transcription Initiation elastin catabolic process fibrillin-1 macrophage chemotaxis valyl-glycyl-valyl-alanyl-prolyl-glycine |
| Content Type | Text |
| Resource Type | Article |
