Rabbit serum alpha‐2‐macroglobulin binds to liver ferritin: association causes a heterogeneity of ferritin molecules

Abstract

Rabbit liver ferritin is unusual since it forms two discrete electrophoretic bands at the beta position of molecular dimers (Santambrogio & Massover, 1987). The present studies have sought to identify the nature of a 170 kDa non-ferritin polypeptide that is uniquely present in the larger beta band. Ultrastructural, immunological and biochemical results all indicate that this polypeptide is a subunit of the plasma protein. alpha-2-macroglobulin. Experimental results show that rabbit serum alpha-2-macroglobulin will bind liver ferritin, and this association induces the de novo formation of the larger beta band. These results thus demonstrate that molecular heterogeneity of ferritin can be caused by its association with a non-ferritin protein. We conclude that alpha-2-macroglobulin is a binder of rabbit tissue ferritin in the circulation; this binding could provide additional means for the receptor-mediated uptake of circulating ferritin.

Identification of Horse Anti-Ferritin Autoantibody

“…It is proposed that an autoantibody to ferritin might be a general ferritin binder along with alpha-2-macroglobuli n [15,22]. In hors es, alpha-2-macroglobulin and fibrinogen have been identified as FBPs [15,19], and these proteins are involved in blood coagulation and plasma fibrinolytic enzyme systems [6,19].…”

“…In addition, horse fibrinogen has been found to be a plasma-specific FBP that inhibits immunoassay of ferritin and binds to horse ferritin [19]. In mammals, although alpha-2-macroglobulin is known to be a common FBP [15,22], anti-ferritin autoantibodies have recently been identified as FBP [17,29]. The purpose of our study was to purify and identify FBPs from horse serum.…”

“…A variety of ferritin-binding proteins (FBPs) in mammalian serum and/or plasma have been described: H-kininogen in human serum [27], alpha-2-macroglobulin in rabbit [22] and horse [15] sera, autoantibodies in canine [29] and bovine [17] sera, and fibrinogen in horse plasma [19]. Although the physiological roles of these FBPs have not been clearly established, FBPs may be involved in the clearance of circulating ferritins following complex formation [5,15,29].…”

Human H-kininogen Is a Ferritin-binding Protein

“…Previous studies have shown that in addition to ferritin, human serum contains ferritinbinding protein(s) (4 -6). In one study, partial purification revealed ferritin binding activity to be present in the ␤-2 region of human serum (6); a study of rabbit serum suggested that ␣ 2 -macroglobulin has ferritin binding activity (7). The role of ferritin-binding proteins(s) is uncertain; however, it has been suggested that ferritin-binding proteins may serve as acquired receptors for ferritin itself.…”

EVALUATION OF SERUM FERRITIN AND SERUM IRON IN FREE-RANGING BLACK RHINOCEROS (DICEROS BICORNIS) AS A TOOL TO UNDERSTAND FACTORS AFFECTING IRON-OVERLOAD DISORDER

“…Such a rapid clearance may be due to interaction with ferritin receptors on hepatocytes (100) which appear to have a higher affinity for liver ferritin than for serum ferritin, at least in experiments on rats. Rapid clearance may also be initiated by interaction with ferritin binding proteins in the plasma (101)(102)(103)(104). Several isoferritins may be released into the plasma but the ones which normally accumulate are L 24 molecules and glycosylated molecules that are rich in L-subunits and again contain little iron.…”