Fibronectin fragments and their role in inflammatory arthritis.
OBJECTIVE
To identify potential immunopathogenic links between fibronectin (Fn) fragmentation and the inflammatory response in chronic joint disease.


METHODS
Scientific papers involving studies of Fn fragments and inflammatory processes important in the pathogenesis of arthritis, including chondrolysis, synoviocyte growth and adhesion, polymorphonuclear leukocyte (PMN) and monocyte function, proteolysis, and immune complex activation were reviewed. In addition, reports identifying Fn fragments in synovial fluid (SF) were assessed.


RESULTS
A series of Fn fragments have been identified in arthritic SF by several investigators. Fn and fragments ranging from 30 to 200 kd are present in elevated concentrations in inflammatory SF. SF Fn fragments display reduced affinity for fibrin and collagen. The 29- and 50-kd amino terminal fragments mediate release of proteoglycan from articular cartilage by RGD-independent mechanisms. Fn fragments can induce fibroblast gene expression of metalloproteinases or can act as proteinases themselves. A 90-kd plasmin generated fragment possesses homology with streptokinase. Fragments mediate PMN chemotaxis and enhance proliferation of CD4+ lymphocytes as well as binding to the C1q component of complement and influencing the behavior of immune complexes.


CONCLUSIONS
Fn fragments can be functionally and biochemically characterized in diseased SF. Modification of fragment formation and inhibition of fragment function may have potential therapeutic value in the interruption of chronic synovial inflammation.
Barilla
M L
ML
Washington University, St Louis, MO, USA.
Carsons
S E
SE
D001168:Arthritis / Q000209:etiology* / Q000276:immunology; D005353:Fibronectins / Q000737:chemistry / Q000502:physiology; D006801:Humans; D010446:Peptide Fragments / Q000502:physiology; D017469:Receptors, Fibronectin / Q000378:metabolism; D013582:Synovial Fluid / Q000737:chemistry
D005353:Fibronectins; D010446:Peptide Fragments; D017469:Receptors, Fibronectin