Article

Emergence of the acute-phase protein hemopexin in jawed vertebrates

Department of Microbiology & Immunology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA.
Molecular Immunology (Impact Factor: 2.97). 09/2010; 48(1-3):147-52. DOI: 10.1016/j.molimm.2010.08.015
Source: PubMed

ABSTRACT

When released from damaged erythrocytes free heme not only provides a source of iron for invading bacteria but also highly toxic due to its ability to catalyze free radical formation. Hemopexin (Hx) binds free heme with very high-affinity and thus protects against heme toxicity, sequesters heme from pathogens, and helps conserve valuable iron. Hx is also an acute-phase serum protein (APP), whose expression is induced by inflammation. To date Hx has been identified as far back in phylogeny as bony fish where it is called warm-temperature acclimation-related 65 kDa protein (WAP65), as serum protein levels are increased at elevated environmental temperatures as well as by infection. During analysis of nurse shark (Ginglymostoma cirratum) plasma we isolated a Ni(2+)-binding serum glycoprotein and characterized it as the APP Hx. We subsequently cloned Hx from nurse shark and another cartilaginous fish species, the little skate Leucoraja erinacea. Functional analysis showed shark Hx, like that of mammals, binds heme but is found at unusually high levels in normal shark serum. As an Hx orthologue could not be found in the genomes of jawless vertebrates or lower deuterostomes it appears to have arisen just prior to the emergence of jawed vertebrates, coincident with the second round of genome-wide duplication and the appearance of tetrameric hemoglobin (Hb).

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    • "Moreover, a SAA counterpart identified from common carp was found to elevate its expression at mRNA level, in response to a turpentine oil treatment in inflammatory leukocytes (Fujiki et al., 2000). Hemopexin was identified as an emerging APP from a cartilaginous fish, nurse shark in a previous study, confirming its heme binding properties (Dooley et al., 2010). Recently, we identified two putative APPs; SAA and Hp from black rockfish, and found that the expression levels of those two genes were markedly induced under a pathogenic stress (Jayasinghe et al., 2015). "
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    ABSTRACT: The basic function of transferrin is to bind iron (III) ions in the medium and to deliver them to the locations where they are required for metabolic processes. It also takes part in the host immune defense mainly via its ability to bind to iron (III) ions. Hence, transferrin is also identified as an important acutephase protein in host immunity. Abalones are major shellfish aquaculture crops that are susceptible to a range of marine microbial infections. Since transferrin is known to be a major player in innate immunity, in the present study we sought to identify, and molecularly and functionally characterize a transferrinlike gene from disk abalone (Haliotis discus discus) named as AbTrf. AbTrf consisted of a 2187-bp open reading frame (ORF) which encodes a 728 amino acid (aa) protein. The putative amino acid sequence of AbTrf harbored N- and C-terminal transferrin-like domains, active sites for iron binding, and conserved cysteine residues. A constitutive tissue specific AbTrf expression pattern was detected by qPCR in abalones where mantle and muscle showed high AbTrf expression levels. Three immune challenge experiments were conducted using Vibrio parahaemolyticus, Listeria monocytogenes and LPS as stimuli and, subsequently, AbTrf mRNA expression levels were quantified in gill and hemocytes in a time-course manner. The mRNA expression was greatly induced in both tissues in response to both challenges. Evidencing the functional property of transferrins, recombinant AbTrf N-terminal domain (AbTrf-N) showed dose-dependent iron (III) binding activity detected by chrome azurol S (CAS) assay system. Moreover, recombinant AbTrf-N could significantly inhibit the growth of iron-dependent bacterium, Escherichia coli in a dose-dependent manner. However, AbTrf-N was unable to show any detectable bacteriostatic activity against iron-independent bacterium Lactobacillus plantarum (L. plantarum) even at its highest concentration. Collectively, our results suggest that AbTrf might play a significant role in the host innate immunity, possibly by withholding iron from pathogens.
    Full-text · Article · Nov 2015 · Developmental & Comparative Immunology
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    • "Moreover, a SAA counterpart identified from common carp was found to elevate its expression at mRNA level, in response to a turpentine oil treatment in inflammatory leukocytes (Fujiki et al., 2000). Hemopexin was identified as an emerging APP from a cartilaginous fish, nurse shark in a previous study, confirming its heme binding properties (Dooley et al., 2010). Recently, we identified two putative APPs; SAA and Hp from black rockfish, and found that the expression levels of those two genes were markedly induced under a pathogenic stress (Jayasinghe et al., 2015). "
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    • "only have 1 copy of the gene. Different studies considered WAP65-2 as an ortholog of the HPX, but this orthology has not been yet fully clarified (Dooley et al. 2010). Further, there has not been any isoform of HPX reported in mammals or in cartilaginous fishes, suggesting that the duplication of the ancestral gene might have occurred after the divergence of teleosts and cartilaginous fishes. "
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