Haptoglobin: A Natural Bacteriostat

Eaton, John W.; Brandt, Paul Dieter; Mahoney, John R.; Lee, James T.

doi:10.1126/science.7036344

Cited by 269 publications

(158 citation statements)

References 14 publications

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“…If limitation of heme source availability contributes to the increased clearance of the ⌬hgp strain from weanling rats, then administration of an exogenous heme source whose utilization is not dependent on Hgp function should enhance the ability of this strain to produce bacteremia. Hemoglobin administration had been shown by others to increase the virulence of pathogenic bacteria in the rat (14). Using the procedure of Eaton et al (14), we first established that intraperitoneal injection of a single hemoglobin dose (20 mg/rat) had no overt adverse clinical effects on the animals as judged by the indices of weight gain, water and food consumption, maintenance of grooming, or activity level (data not shown).…”

Section: Vol 74 2006 Role Of H Influenzae Hgp Genes In Invasive DImentioning

confidence: 97%

Complex Role of Hemoglobin and Hemoglobin-Haptoglobin Binding Proteins in Haemophilus influenzae Virulence in the Infant Rat Model of Invasive Infection

Seale¹,

Morton²,

Whitby³

et al. 2006

Infect Immun

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Haemophilus influenzae requires an exogenous heme source for aerobic growth in vitro. Hemoglobin or hemoglobin-haptoglobin satisfies this requirement. Heme acquisition from hemoglobin-haptoglobin is mediated by proteins encoded by hgp genes. Both Hgps and additional proteins, including those encoded by the hxu operon, provide independent pathways for hemoglobin utilization. Recently we showed that deletion of the set of three hgp genes from a nontypeable strain (86-028NP) of H. influenzae attenuated virulence in the chinchilla otitis media model of noninvasive disease. The present study was undertaken to investigate the role of the hgp genes in virulence of the wild-type serotype b clinical isolate HI689 in the infant rat model of hematogenous meningitis, an established model of invasive disease requiring aerobic growth. Bacteremia of high titer and long duration (>14 days) and histopathologically confirmed meningitis occurred in >95% of infant rats challenged at 5 days of age with strain HI689. While mutations disrupting either the Hgp-or Hxu-mediated pathway of heme acquisition had no effect on virulence in infant rats, an isogenic mutant deficient for both pathways was unable to sustain bacteremia or produce meningitis. In contrast, mutations disrupting either pathway decreased the limited ability of H. influenzae to initiate and sustain bacteremia in weanling rats. Biochemical and growth studies also indicated that infant rat plasma contains multiple heme sources that change with age. Taken together, these data indicate that both the hgp genes and the hxuC gene are virulence determinants in the rat model of human invasive disease.

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Section: Vol 74 2006 Role Of H Influenzae Hgp Genes In Invasive DImentioning

confidence: 97%

Complex Role of Hemoglobin and Hemoglobin-Haptoglobin Binding Proteins in Haemophilus influenzae Virulence in the Infant Rat Model of Invasive Infection

Seale¹,

Morton²,

Whitby³

et al. 2006

Infect Immun

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“…In cows with fatty liver, concentrations of lipoprotein lipids and apoproteins including apoA-I are decreased [14]. The lipoprotein Hp, singly or in combination with Hb and/or apoA-I, may act as a bacteriostat [3] or, although controversial, an inhibitor for neutrophil functions [16]. The elucidation of the functional relevance of lipoprotein Hp may shed light on the mechanism of the cross talk between the acute-phase response and lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Analysis by Enzyme-Linked Immunosorbent Assay and 2-Dimensional Electrophoresis of Haptoglobin in the High-Density Lipoprotein Fraction in Cows.

Kanno

Katoh

2001

J. Vet. Med. Sci.

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ABSTRACT. Haptoglobin (Hp) is a hemoglobin (Hb)-binding acute-phase protein. Besides its relevance in inflammation, Hp is involved in the regulation of lipid metabolism. In cattle, in addition to the lipoprotein-deficient fraction, Hp is distributed in high-density lipoprotein (HDL) and very high-density lipoprotein (VHDL) fractions. The purpose of this study was to determine Hp concentrations in the lipoprotein fractions using an enzyme-linked immunosorbent assay (ELISA) based on the affinity with Hb, and also to detect structural differences of HDL Hp from that in the lipoprotein-deficient fraction using 2-dimensional electrophoresis. When purified Hp was used as the antigen for the ELISA, the detection limit was 7.4 ng/ml and linearity was obtained from 14.8 to 475 ng/ml. The correlation coefficient between the ELISA and single radial immunodiffusion was 0.884. The ELISA was shown to be applicable to evaluate Hp concentrations in the lipoprotein fractions. Hp concentrations in the lipoprotein fractions were in the range of 0.94 to 8.77 µg of Hp/ml (n=4), and concentration ratios were 0.2 to 0.3% of whole serum Hp. Of the lipoprotein fractions, Hp was most abundant in HDL, moderate in VHDL and faint in chylomicrons, the very low-density lipoprotein fraction and low-density lipoprotein fraction. By 2-dimensional electrophoresis, α-and β-chains of serum Hp were each separated into 5 spots, and their isoelectric point (pI) values were from 5.05 to 6.28 in the α-chain and from 5.92 to 6.95 in the β-chain. The pI values of HDL Hp were indistinguishable from those of serum Hp. These results indicate that the ELISA based on the affinity with Hb is useful for evaluating Hp concentrations in lipoprotein fractions, and also suggest that HDL Hp is structurally similar to that in the lipoprotein-deficient fraction. KEY WORDS: bovine, enzyme-linked immunosorbent assay, haptoglobin, high-density lipoprotein, 2-dimensional electrophoresis.

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“…Haptoglobin is known to have a bacteriostatic effect on Escherischia coli due to its ability to bind hemoglobin [22] and thus it may affect the uptake of nutrients by P. falciparum in an analogous manner. P. falciparum produces complex membranous structures within the host cell cytoplasm, including flattened lamaellae called Maurer's clefts which are implicated in the transport of parasite proteins to the erythrocyte plasma membrane and submembrane skeleton [23]. The appearance of electron-dense material (at present unidentified) in Maurer's clefts following incubation with haptoglobin suggests that it interferes with protein trafficking.…”

Section: Discussionmentioning

confidence: 99%

Human serum haptoglobin is toxic to Plasmodium falciparum in vitro

Imrie

Ferguson

Day

2004

Molecular and Biochemical Parasitology

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Innate immune responses are important in the control of malaria, particularly in those who have not yet mounted an effective adaptive response. Here we report that the human serum acute phase protein, haptoglobin is toxic to Plasmodium falciparum cultured in vitro. This effect is phenotype-dependent and occurs during the trophozoite phase of the asexual life cycle. We propose that the increased levels of haptoglobin seen in the acute phase response may be protective against malaria in humans.

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Haptoglobin: A Natural Bacteriostat

Cited by 269 publications

References 14 publications

Complex Role of Hemoglobin and Hemoglobin-Haptoglobin Binding Proteins in Haemophilus influenzae Virulence in the Infant Rat Model of Invasive Infection

Complex Role of Hemoglobin and Hemoglobin-Haptoglobin Binding Proteins in Haemophilus influenzae Virulence in the Infant Rat Model of Invasive Infection

Analysis by Enzyme-Linked Immunosorbent Assay and 2-Dimensional Electrophoresis of Haptoglobin in the High-Density Lipoprotein Fraction in Cows.

Human serum haptoglobin is toxic to Plasmodium falciparum in vitro

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