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A key role for Fut1-regulated angiogenesis and ICAM-1 expression in K/BxN arthritis
  1. Mohammad A Amin1,
  2. Phillip L Campbell1,
  3. Jeffrey H Ruth1,
  4. Takeo Isozaki1,
  5. Bradley J Rabquer1,
  6. W Alex Stinson1,
  7. Martin O'Brien1,
  8. Gautam Edhayan1,
  9. Ray A Ohara1,
  10. Jonathon Vargo1,
  11. Steven E Domino2,
  12. Alisa E Koch1,3
  1. 1Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
  2. 2Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, Michigan, USA
  3. 3Veteran's Administration, Ann Arbor, Michigan, USA
  1. Correspondence to Dr Mohammad A Amin, Department of Internal Medicine/Division of Rheumatology, University of Michigan Medical School, 4428 BSRB, 109 Zina Pitcher Drive, Ann Arbor, MI 48109-2200, USA; maamin{at}


Objectives Angiogenesis contributes to the pathogenesis of rheumatoid arthritis. Fucosyltransferases (Futs) are involved in angiogenesis and tumour growth. Here, we examined the role of Fut1 in angiogenesis and K/BxN serum transfer arthritis.

Methods We examined Fut1 expression in human dermal microvascular endothelial cells (HMVECs) by quantitative PCR. We performed a number of angiogenesis assays to determine the role of Fut1 using HMVECs, Fut1 null (Fut1−/−), and wild type (wt) endothelial cells (ECs) and mice. K/BxN serum transfer arthritis was performed to determine the contribution of Fut1-mediated angiogenesis in Fut1−/− and wt mice. A static adhesion assay was implemented with RAW264.7 (mouse macrophage cell line) and mouse ECs. Quantitative PCR, immunofluorescence and flow cytometry were performed with Fut1−/− and wt ECs for adhesion molecule expression.

Results Tumour necrosis factor-α induced Fut1 mRNA and protein expression in HMVECs. HMVECs transfected with Fut1 antisense oligodeoxynucleotide and Fut1−/− ECs formed significantly fewer tubes on Matrigel. Fut1−/− mice had reduced angiogenesis in Matrigel plug and sponge granuloma angiogenesis assays compared with wt mice. Fut1−/− mice were resistant to K/BxN serum transfer arthritis and had decreased angiogenesis and leucocyte ingress into inflamed joints. Adhesion of RAW264.7 cells to wt mouse ECs was significantly reduced when Fut1 was lacking. Fut1−/− ECs had decreased intercellular adhesion molecule-1 (ICAM-1) expression at mRNA and protein levels compared with wt ECs. ICAM-1 was also decreased in Fut1−/− arthritic ankle cryosections compared with wt ankles.

Conclusions Fut1 plays an important role in regulating angiogenesis and ICAM-1 expression in inflammatory arthritis.

  • Arthritis
  • Inflammation
  • Rheumatoid Arthritis

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