Heme and innate immunity: new insights for an old molecule

Arruda, Maria Augusta; Graça-Souza, Aurélio V.; Barja‐Fidalgo, Christina

doi:10.1590/s0074-02762005000700022

Cited by 15 publications

(11 citation statements)

References 37 publications

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“…Lyoumi et al (1999) also suggested that haeme can boost the expression of positive acute-phase reactants in rats during an infl ammatory challenge, which indicated that haeme can positively affect the immune function of animals. Similarly, Arruda et al (2005) suggested haeme can be considered a proinfl ammatory molecule, which may play a central role during the onset and/or persistence of infl ammation. Secondly, immunity may affected by improved iron status.…”

Section: Discussionmentioning

confidence: 99%

Utilization of δ-aminolevulinic acid for livestock: blood characteristics and immune organ weight in broilers

et al. 2008

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A study was conducted to evaluate the effects of δ-aminolevulinic acid (ALA) on blood characteristics and immune organ weight in broilers. One-day-old broiler chicks were randomly assigned to one of four dietary treatments with six replicates of 20 chickens each. Treatments were basal diet supplemented with 0, 5, 10 and 15 mg/kg ALA. The two-phase experimental diets were formulated to meet the NRC requirements for chicks and fed for 5 weeks. Growth performance was not affected by supplementation of ALA during any of the experimental periods. Blood cell counts (WBC, RBC and lymphocyte), serum total protein, albumin, iron concentrations, and total iron binding capacity (TIBC) were also not infl uenced by dietary treatments. Haemoglobin concentration tended to increase with an increased ALA supplementation level (linear effect; P<0.10). Dietary ALA addition did not infl uence liver weight. However, spleen and bursa of fabricius weights were increased with the increased ALA supplementation level (linear effect; P<0.05). The current data indicate that supplementation of ALA in commercial broiler diets could partly improve haemoglobin concentration and immune organ weights, without infl uencing growth performance and other blood characteristics of broilers.

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Section: Discussionmentioning

confidence: 99%

Utilization of δ-aminolevulinic acid for livestock: blood characteristics and immune organ weight in broilers

et al. 2008

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“…Heme could be released in large amounts as a result of many pathological conditions such as hemolysis, rhabdomyolysis, hemoglobinopathies, ischemia/ reperfusion, malaria, severe inflammation, etc. (2)(3)(4)(5)(6)(7)(8). Usually under these conditions, the systems that protect the organism from free heme toxicity are saturated, and high plasma concentrations of this pro-oxidative molecule are reached (more than 20 M).…”

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confidence: 99%

Antibodies Use Heme as a Cofactor to Extend Their Pathogen Elimination Activity and to Acquire New Effector Functions

Dimitrov

Roumenina

Doltchinkova

et al. 2007

Journal of Biological Chemistry

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Various pathological processes are accompanied by release of high amounts of free heme into the circulation. We demonstrated by kinetic, thermodynamic, and spectroscopic analyses that antibodies have an intrinsic ability to bind heme. This binding resulted in a decrease in the conformational freedom of the antibody paratopes and in a change in the nature of the noncovalent forces responsible for the antigen binding. The antibodies use the molecular imprint of the heme molecule to interact with an enlarged panel of structurally unrelated epitopes. Upon heme binding, monoclonal as well as pooled immunoglobulin G gained an ability to interact with previously unrecognized bacterial antigens and intact bacteria. IgG-heme complexes had an enhanced ability to trigger complement-mediated bacterial killing. It was also shown that heme, bound to immunoglobulins, acted as a cofactor in redox reactions. The potentiation of the antibacterial activity of IgG after contact with heme may represent a novel and inducible innate-type defense mechanism against invading pathogens.

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“…I ntravascular lysis of erythrocytes is associated with a number of pathologic conditions and can lead to release into the bloodstream of substantial amounts of hemoglobin and its breakdown products, including hematin (Fe III protoporphyrin IX) (1)(2)(3)(4). Both free hemoglobin and hematin can promote severe tissue injury at a variety of sites, and several mechanisms serve to protect the body from these inflammatory agents (2)(3)(4)(5)(6)(7)(8).…”

mentioning

confidence: 99%

“…Both free hemoglobin and hematin can promote severe tissue injury at a variety of sites, and several mechanisms serve to protect the body from these inflammatory agents (2)(3)(4)(5)(6)(7)(8). Under quiescent conditions, hemoglobin or hematin released into the circulation are rapidly sequestered by haptoglobin and hemopexin, respectively, and then cleared by the liver, thus preventing the buildup of these toxic agents in the blood (3,7).…”

mentioning

confidence: 99%

“…Under quiescent conditions, hemoglobin or hematin released into the circulation are rapidly sequestered by haptoglobin and hemopexin, respectively, and then cleared by the liver, thus preventing the buildup of these toxic agents in the blood (3,7). However, under pathologic conditions in diseases such as paroxysmal nocturnal hemoglobinuria or malaria, these defense mechanisms may be overwhelmed by the release of large amounts of erythrocyte breakdown products, and due to the failure to neutralize these agents, secondary pathologies may ensue (2)(3)(4)9). Malaria-associated anemia in young children is further complicated because, in many cases, the number of erythrocytes that are lost far exceeds the number of erythrocytes that are actually infected by the Plasmodium falciparum (Pf) 3 parasite (10 -16).…”

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confidence: 99%

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Hematin Promotes Complement Alternative Pathway-Mediated Deposition of C3 Activation Fragments on Human Erythrocytes: Potential Implications for the Pathogenesis of Anemia in Malaria

Pawluczkowycz

Lindorfer

Waitumbi

et al. 2007

The Journal of Immunology

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Childhood malaria caused by Plasmodium falciparum is often characterized by severe anemia at low parasite burdens; the mechanism(s) responsible for this pathology remain to be defined. We have reported, based on clinical observations and in vitro models, that complement control proteins on erythrocytes such as CR1, the immune adherence receptor specific for C3b, may be reduced in childhood malaria, suggesting a possible role for complement in erythrocyte destruction. Intravascular lysis of iE by P. falciparum leads to release of erythrocyte breakdown products such as hemoglobin and hematin, which have inflammatory properties. In the present article, we demonstrate that in serum and in anticoagulated whole blood, moderate concentrations of hematin activate the alternative pathway of complement and promote deposition of C3 activation and breakdown products on erythrocytes. The degree of C3 fragment deposition is directly correlated with erythrocyte CR1 levels, and erythrocytes opsonized with large amounts of C3dg form rosettes with Raji cells, which express CR2, the C3dg receptor which is expressed on several types of B cells in the spleen. Thus, the reaction mediated by hematin promotes opsonization and possible clearance of the youngest (highest CR1) erythrocytes. A mAb specific for C3b, previously demonstrated to inhibit the alternative pathway of complement, completely blocks the C3 fragment deposition reaction. Use of this mAb in nonhuman primate models of malaria may provide insight into mechanisms of erythrocyte destruction and thus aid in the development of targeted therapies based on inhibiting the alternative pathway of complement.

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Heme and innate immunity: new insights for an old molecule

Cited by 15 publications

References 37 publications

Utilization of δ-aminolevulinic acid for livestock: blood characteristics and immune organ weight in broilers

Utilization of δ-aminolevulinic acid for livestock: blood characteristics and immune organ weight in broilers

Antibodies Use Heme as a Cofactor to Extend Their Pathogen Elimination Activity and to Acquire New Effector Functions

Hematin Promotes Complement Alternative Pathway-Mediated Deposition of C3 Activation Fragments on Human Erythrocytes: Potential Implications for the Pathogenesis of Anemia in Malaria

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