Induction of macrophage chemotaxis by aortic extracts of the mgR marfan mouse model and a GxxPG-containing fibrillin-1 fragment

Gao Guo, Patrick Booms, Marc Halushka, Harry C. Dietz, Andreas Ney, Sigmar Stricker, Jochen Hecht, Stefan Mundlos, Peter N. Robinson

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1855-1862
Number of pages8
Issue number17
StatePublished - Oct 2006


  • Chemotaxis
  • Elastin-binding proteins
  • Fibrillin
  • Marfan syndrome

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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