title: Hemoglobin enhances the biological activity of synthetic and natural bacterial (endotoxic) virulence factors: a general principle.
abstract: Although hemoglobin (Hb) is mainly present in the cytoplasm of erythrocytes (red blood cells), lower concentrations of pure, cell-free Hb are released permanently into the circulation due to an inherent intravascular hemolytic disruption of erythrocytes. Previously it was shown that the interaction of Hb with bacterial endotoxins (lipopolysaccharides, LPS) results in a significant increase of the biological activity of LPS. There is clear evidence that the enhancement of the biological activity of LPS by Hb is connected with a disaggregation of LPS. From these findings one questions whether the property to enhance the biological activity of endotoxin, in most cases proven by the ability to increase the cytokine (tumor-necrosis-factor-alpha, interleukins) production in human mononuclear cells, is restricted to bacterial endotoxin or is a more general principle in nature. To elucidate this question, we investigated the interaction of various synthetic and natural virulence (pathogenicity) factors with hemoglobin of human or sheep origin. In addition to enterobacterial R-type LPS a synthetic bacterial lipopeptide and synthetic phospholipid-like structures mimicking the lipid A portion of LPS were analysed. Furthermore, we also tested endotoxically inactive LPS and lipid A compounds such as those from Chlamydia trachomatis. We found that the observations made for endotoxically active form of LPS can be generalized for the other synthetic and natural virulence factors: In every case, the cytokine-production induced by them is increased by the addition of Hb. This biological property of Hb is connected with its physical property to convert the aggregate structures of the virulence factors into one with cubic symmetry, accompanied with a considerable reduction of the size and number of the original aggregates.
authors.affiliation: Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, 23845 Borstel, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Howe
authors.forename: Walter
authors.initials: W
authors.lastname: Richter
authors.forename: Lynn
authors.initials: L
authors.lastname: Hawkins
authors.forename: Manfred
authors.initials: M
authors.lastname: Rössle
authors.forename: Christian
authors.initials: C
authors.lastname: Alexander
authors.forename: Karin
authors.initials: K
authors.lastname: Fournier
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Mach
authors.forename: Thierry
authors.initials: T
authors.lastname: Waelli
authors.forename: Reginald M
authors.initials: RM
authors.lastname: Gorczynski
authors.forename: Artur J
authors.initials: AJ
authors.lastname: Ulmer
authors.forename: Helmut
authors.initials: H
authors.lastname: Brade
authors.forename: Alla
authors.initials: A
authors.lastname: Zamyatina
authors.forename: Paul
authors.initials: P
authors.lastname: Kosma
authors.forename: Ernst Th
authors.initials: ET
authors.lastname: Rietschel
authors.forename: Klaus
authors.initials: K
authors.lastname: Brandenburg
mesh_terms: D000818:Animals; D002241:Carbohydrates / Q000737:chemistry; D016207:Cytokines / Q000096:biosynthesis; D005614:Freeze Fracturing; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008055:Lipids / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism; D012475:Salmonella / Q000737:chemistry; D012756:Sheep; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D013696:Temperature; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D037521:Virulence Factors / Q000737:chemistry / Q000494:pharmacology*; D014961:X-Ray Diffraction
chemical_list: D002241:Carbohydrates; D016207:Cytokines; D006454:Hemoglobins; D008055:Lipids; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D037521:Virulence Factors