Hemoglobin enhances the biological activity of synthetic and natural bacterial (endotoxic) virulence factors: a general principle.
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.
Howe
Jörg
J
Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, 23845 Borstel, Germany.
Richter
Walter
W
Hawkins
Lynn
L
Rössle
Manfred
M
Alexander
Christian
C
Fournier
Karin
K
Mach
Jean Pierre
JP
Waelli
Thierry
T
Gorczynski
Reginald M
RM
Ulmer
Artur J
AJ
Brade
Helmut
H
Zamyatina
Alla
A
Kosma
Paul
P
Rietschel
Ernst Th
ET
Brandenburg
Klaus
K
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
D002241:Carbohydrates; D016207:Cytokines; D006454:Hemoglobins; D008055:Lipids; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D037521:Virulence Factors