scholarly journals Serum Amyloid P Component Is the Shiga Toxin 2-neutralizing Factor in Human Blood

2001 ◽  
Vol 276 (45) ◽  
pp. 41576-41579 ◽  
Author(s):  
Tsuyoshi Kimura ◽  
Shinobu Tani ◽  
Yoh-ichi Matsumoto ◽  
Tae Takeda
Keyword(s):  
Human Blood ◽  
Shiga Toxin ◽  
Serum Amyloid ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Shiga Toxin 2 ◽  
Amyloid P

scholarly journals Lipopolysaccharide Renders Transgenic Mice Expressing Human Serum Amyloid P Component Sensitive to Shiga Toxin 2

PLoS ONE ◽  
2011 ◽  
Vol 6 (6) ◽  
pp. e21457 ◽  
Author(s):  
Thomas P. Griener ◽  
Jonathan G. Strecker ◽  
Romney M. Humphries ◽  
George L. Mulvey ◽  
Carmen Fuentealba ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Human Serum ◽  
Shiga Toxin ◽  
Serum Amyloid ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Shiga Toxin 2 ◽  
Amyloid P

scholarly journals Serum Amyloid P Component Binding to Shiga Toxin 2 Requires Both A Subunit and B Pentamer

2003 ◽  
Vol 71 (10) ◽  
pp. 6075-6078 ◽  
Author(s):  
Paola Marcato ◽  
Kathleen Vander Helm ◽  
George L. Mulvey ◽  
Glen D. Armstrong
Keyword(s):  
Shiga Toxin ◽  
Solid Phase ◽  
Serum Amyloid ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Shiga Toxin 2 ◽  
A Subunit ◽  
Globotriaosyl Ceramide ◽  
Solid Phase Binding ◽  
Amyloid P

ABSTRACT Solid-phase binding, competitive binding, and cytotoxicity neutralization assays indicate that the B pentamer and A subunit both contribute to human serum amyloid P (HuSAP) component binding to Stx2. A polyvalent globotriaosyl-ceramide receptor analog, Daisy, did not competitively inhibit HuSAP binding, implying that the two ligands bind to different Stx2 domains.

scholarly journals Human Serum Amyloid P Component Protects againstEscherichia coliO157:H7 Shiga Toxin 2 In Vivo: Therapeutic Implications for Hemolytic‐Uremic Syndrome

2006 ◽  
Vol 193 (8) ◽  
pp. 1120-1124 ◽  
Author(s):  
Glen D. Armstrong ◽  
George L. Mulvey ◽  
Paola Marcato ◽  
Thomas P. Griener ◽  
Melvyn C. Kahan ◽  
...  
Keyword(s):  
Human Serum ◽  
Shiga Toxin ◽  
Amyloid P Component ◽  
Therapeutic Implications ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Shiga Toxin 2 ◽  
Uremic Syndrome ◽  
Amyloid P

scholarly journals Protection of Human Podocytes from Shiga Toxin 2-Induced Phosphorylation of Mitogen-Activated Protein Kinases and Apoptosis by Human Serum Amyloid P Component

2014 ◽  
Vol 82 (5) ◽  
pp. 1872-1879 ◽  
Author(s):  
Anne K. Dettmar ◽  
Elisabeth Binder ◽  
Friederike R. Greiner ◽  
Max C. Liebau ◽  
Christine E. Kurschat ◽  
...  
Keyword(s):  
Human Serum ◽  
Protein Kinases ◽  
Shiga Toxin ◽  
Mitogen Activated Protein Kinases ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Mitogen Activated Protein ◽  
Shiga Toxin 2 ◽  
Amyloid P

ABSTRACTHemolytic uremic syndrome (HUS) is mainly induced by Shiga toxin 2 (Stx2)-producingEscherichia coli. Proteinuria can occur in the early phase of the disease, and its persistence determines the renal prognosis. Stx2 may injure podocytes and induce proteinuria. Human serum amyloid P component (SAP), a member of the pentraxin family, has been shown to protect against Stx2-induced lethality in micein vivo, presumably by specific binding to the toxin. We therefore tested the hypothesis that SAP can protect against Stx2-induced injury of human podocytes. To elucidate the mechanisms underlying podocyte injury in HUS-associated proteinuria, we assessed Stx2-induced activation of mitogen-activated protein kinases (MAPKs) and apoptosis in immortalized human podocytes and evaluated the impact of SAP on Stx2-induced damage. Human podocytes express Stx2-binding globotriaosylceramide 3. Stx2 applied to cultured podocytes was internalized and then activated p38α MAPK and c-Jun N-terminal kinase (JNK), important signaling steps in cell differentiation and apoptosis. Stx2 also activated caspase 3, resulting in an increased level of apoptosis. Coincubation of podocytes with SAP and Stx2 mitigated the effects of Stx2 and induced upregulation of antiapoptotic Bcl2. These data suggest that podocytes are a target of Stx2 and that SAP protects podocytes against Stx2-induced injury. SAP may therefore be a useful therapeutic option.

scholarly journals Lipopolysaccharide (LPS)-Binding Synthetic Peptides Derived from Serum Amyloid P Component Neutralize LPS

1999 ◽  
Vol 67 (6) ◽  
pp. 2790-2796 ◽  
Author(s):  
Carla J. C. de Haas ◽  
Ruurd van der Zee ◽  
Barry Benaissa-Trouw ◽  
Kok P. M. van Kessel ◽  
Jan Verhoef ◽  
...  
Keyword(s):  
Amino Acids ◽  
Septic Shock ◽  
Human Blood ◽  
Serum Amyloid ◽  
Gram Negative ◽  
Amyloid P Component ◽  
Serum Amyloid P ◽  
Serum Amyloid P Component ◽  
Amyloid P ◽  
Lps Binding

ABSTRACT Lipopolysaccharide (LPS) is the major mediator of gram-negative septic shock. Molecules that bind LPS and neutralize its toxic effects could have important clinical applications. We showed that serum amyloid P component (SAP) neutralizes LPS. A SAP-derived peptide, consisting of amino acids 27 to 39, inhibited LPS-mediated effects in the presence of human blood. In this study, we used a pepscan of overlapping 15-mer peptides and distinguished two additional LPS-binding regions within the SAP molecule, identified in the regions spanning amino acids 61 to 75 and 186 to 200. The corresponding SAP-derived peptides, pep61-75 and pep186-200, inhibited the binding of fluorescein isothiocyanate-labeled LPS to monocytes as efficiently as a bactericidal/permeability-increasing protein (BPI)-derived 15-mer peptide comprising amino acids 85 to 99. The same SAP-derived peptides very potently inhibited LPS-induced priming of phagocytes in human blood. Also, SAP-derived pep186-200 caused a prolonged survival of actinomycin D-sensitized mice treated with LPS to induce septic shock, indicating a potential use of this peptide in the defense against serious gram-negative sepsis in humans.

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