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Heme Interferes Wit...
Heme Interferes With Complement Factor I-Dependent Regulation by Enhancing Alternative Pathway Activation
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- Gerogianni, Alexandra (author)
- Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Linnaeus Ctr Biomat Chem, BMC,Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden.;Linnaeus Univ, Dept Chem & Biomed, Kalmar, Sweden
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- Dimitrov, Jordan D. (author)
- Sorbonne Univ, Univ Paris, Ctr Rech Cordeliers, INSERM, Paris, France
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- Zarantonello, Alessandra (author)
- Sorbonne Univ, Univ Paris, Ctr Rech Cordeliers, INSERM, Paris, France
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- Poillerat, Victoria (author)
- Sorbonne Univ, Univ Paris, Ctr Rech Cordeliers, INSERM, Paris, France
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- Chonat, Satheesh (author)
- Childrens Healthcare Atlanta, Aflac Canc & Blood Disorders Ctr, Atlanta, GA USA.;Emory Univ, Dept Pediat, Sch Med, Atlanta, GA USA
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- Sandholm, Kerstin (author)
- Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Linnaeus Univ, Dept Chem & Biomed, Kalmar, Sweden
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- McAdam, Karin E. (author)
- Oslo Univ Hosp, Dept Immunol, Oslo, Norway.;Univ Oslo, Oslo, Norway
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- Nilsson Ekdahl, Kristina (author)
- Uppsala universitet,Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Uppsala University, Sweden,Linnaeus Ctr Biomat Chem, BMC,Klinisk immunologi,Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden.;Linnaeus Univ, Dept Chem & Biomed, Kalmar, Sweden
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- Mollnes, Tom E. (author)
- Oslo Univ Hosp, Dept Immunol, Oslo, Norway.;Univ Oslo, Oslo, Norway.;Norwegian Univ Sci & Technol, Ctr Mol Inflammat Res, Trondheim, Norway.;Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.;Nordland Hosp, Res Lab, Bodo, Norway
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- Mohlin, Camilla, 1972- (author)
- Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Linnaeus Ctr Biomat Chem, BMC,Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden.;Linnaeus Univ, Dept Chem & Biomed, Kalmar, Sweden
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- Roumenina, Lubka T. (author)
- Sorbonne Univ, Univ Paris, Ctr Rech Cordeliers, INSERM, Paris, France
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- Nilsson, Per H., 1980- (author)
- Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Avancerade material,Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden.;Linnaeus Univ, Dept Chem & Biomed, Kalmar, Sweden.;Oslo Univ Hosp, Dept Immunol, Oslo, Norway.;Univ Oslo, Oslo, Norway,Linnaeus Ctr Biomat Chem, BMC;HoRB
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(creator_code:org_t)
- 2022-07-22
- 2022
- English.
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 13
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Abstract
Subject headings
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- Hemolysis, as a result of disease or exposure to biomaterials, is characterized by excess amounts of cell-free heme intravascularly and consumption of the protective heme-scavenger proteins in plasma. The liberation of heme has been linked to the activation of inflammatory systems, including the complement system, through alternative pathway activation. Here, we investigated the impact of heme on the regulatory function of the complement system. Heme dose-dependently inhibited factor I-mediated degradation of soluble and surface-bound C3b, when incubated in plasma or buffer with complement regulatory proteins. Inhibition occurred with factor H and soluble complement receptor 1 as co-factors, and the mechanism was linked to the direct heme-interaction with factor I. The heme-scavenger protein hemopexin was the main contaminant in purified factor I preparations. This led us to identify that hemopexin formed a complex with factor I in normal human plasma. These complexes were significantly reduced during acute vasoocclusive pain crisis in patients with sickle cell disease, but the complexes were normalized at their baseline outpatient clinic visit. Hemopexin exposed a protective function of factor I activity in vitro, but only when it was present before the addition of heme. In conclusion, we present a mechanistic explanation of how heme promotes uncontrolled complement alternative pathway amplification by interfering with the regulatory capacity of factor I. Reduced levels of hemopexin and hemopexin-factor I complexes during an acute hemolytic crisis is a risk factor for heme-mediated factor I inhibition.
Subject headings
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
Keyword
- heme
- complement
- factor I
- co-factor activity
- hemopexin
- hemolysis
- Immunologi
- Immunology
Publication and Content Type
- ref (subject category)
- art (subject category)
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Gerogianni, Alex ...
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Dimitrov, Jordan ...
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Zarantonello, Al ...
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Poillerat, Victo ...
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Chonat, Satheesh
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Sandholm, Kersti ...
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McAdam, Karin E.
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Nilsson Ekdahl, ...
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Mollnes, Tom E.
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Mohlin, Camilla, ...
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Roumenina, Lubka ...
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Nilsson, Per H., ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Immunology
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Microbiology
- Articles in the publication
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Frontiers in Imm ...
- By the university
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Linnaeus University
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Uppsala University