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Plasma ferritin is an important extracellular iron storage molecule, whose concentration increases drastically in cancer and infection. During infection, the pathogen usurps host iron for its survival and pathogenicity; hence, maintenance of the plasma ferritin level during infection is a crucial host defence mechanism. In this study, the horseshoe crab plasma ferritin complex was purified, characterized, and its involvement in innate immune defence was investigated. The plasma ferritin appears as a 21-kDa subunit on SDS-PAGE. Full-length ferritin-H cDNAs (CrFer-H1 and CrFer-H2) were cloned. Analysis of the 5' UTR indicates the existence of a functional iron-response element, suggesting that both the CrFer-H genes may be post-transcriptionally regulated. Northern analysis shows that the CrFer-H is ubiquitously expressed. Within 3 h of lipopolysaccharide challenge, the gene is up-regulated by > 12-fold. In contrast, iron-loading did not result in any significant change. When challenged with Pseudomonas aeruginosa, the plasma ferritin disappeared between 6-48 h and re-appeared thereafter, suggesting that during infection, ferritin may be concealed intracellularly as it withholds iron from the invading pathogen. Taken together, these results provide insights into the importance of plasma ferritin as an evolutionarily conserved molecule for the iron-withholding strategy of innate immunity.

Original publication

DOI

10.1179/096805105x58698

Type

Journal article

Journal

Journal of endotoxin research

Publication Date

01/2005

Volume

11

Pages

267 - 280

Addresses

Department of Biological Sciences, National University of Singapore, Singapore.

Keywords

Animals, Horseshoe Crabs, Pseudomonas aeruginosa, Pseudomonas Infections, Acute Disease, Lipopolysaccharides, Electrophoresis, Polyacrylamide Gel, Amino Acid Sequence, Base Sequence, Molecular Sequence Data, Ferritins, Immunity, Innate