Blocking platelet/endothelial cell adhesion molecule 1 (PECAM) inhibits disease progression and prevents joint erosion in established collagen antibody-induced arthritis.
Collagen antibody-induced arthritis is a robust murine model of arthritis that histologically recapitulates the inflammatory characteristics of rheumatoid arthritis including pannus formation and destruction of articular cartilage and bone. PECAM is a molecule expressed by both leukocytes and endothelial cells that has been shown to play a major role in the extravasation of leukocytes into sites of inflammation. Genetic deletion of many molecules will blunt the onset and progression of arthritis in murine models, as will administration of various anti-inflammatory therapies given prior to the onset of disease. However, patients seek medical attention when symptomatic, which means that the disease is well established. We investigated whether blocking PECAM interactions would inhibit progression of established disease in the collagen antibody-induced arthritis model. We report that treatment of symptomatic mice with a PECAM-Fc chimera significantly reduced inflammation and virtually eliminated cartilage and bone destruction. The results suggest that therapies that block PECAM function may be beneficial in the treatment of established arthritis.
Department of Pathology, Northwestern University Feinberg School of Medicine, Ward Building 3-140, 303 E. Chicago Avenue, Chicago, IL 60611, USA.
Bidisha
B
Dasgupta
Tina
T
Chew
Alana
A
deRoche
William A
WA
Muller
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology*; D007596:Joints / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000187:drug effects* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D013585:Synovitis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D007141:Immunoglobulin Fc Fragments; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011993:Recombinant Fusion Proteins