The role of fibronectin in the development of experimental amyloidosis. Evidence of immunohistochemical codistribution and binding property with serum amyloid protein A.
Azocasein-induced amyloid A (AA) amyloidosis in CBA/K1Jms mice was investigated to elucidate a preference of serum amyloid A (SAA) deposition in the spleen. By indirect immunofluorescence using anti-SAA/AA antibodies the initial deposition of SAA/AA was recognized in the marginal zone of spleen at 20 days after azocasein injection. Indirect immunofluorescence using anti-fibronectin antibodies also showed meshwork positivity in the corresponding area more intensely than that in controls. Immunoelectron microscopy using anti-SAA/AA revealed the presence of positively stained flocculent materials on cell surfaces of macrophages in the marginal area in addition to amyloid fibril. The tissue fibronectin rapidly increased in the spleen and maintained 10 times more than that of controls until the 20th day. Binding assay of SAA on frozen sections revealed the presence of SAA-binding substances in the perifollicular area. Affinity chromatographic assay showed fibronectin have a binding capacity to SAA1 and SAA2. By binding assay on the microtiter plate, SAA had more affinity to fibronectin than those of heparan sulfate, collagen type I, or serum amyloid P component. These results indicate that fibronectin plays an important role in the development of amyloidosis by working as a linking protein between SAA and the cell surface of macrophages.
Kawahara
E
E
Department of Pathology, School of Medicine, Kanzawa University Japan.
Shiroo
M
M
Nakanishi
I
I
Migita
S
S
D000686:Amyloidosis / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D002364:Caseins; D003094:Collagen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism / Q000502:physiology*; D006497:Heparan Sulfate / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D012710:Serum Albumin, Bovine / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism / Q000473:pathology
D002364:Caseins; D003094:Collagen; D005353:Fibronectins; D006497:Heparan Sulfate; D012710:Serum Albumin, Bovine; D000685:Serum Amyloid A Protein; C026018:azocasein