Curvature of Synthetic and Natural Surfaces is an Important Target Feature in Classical Pathway Complement Activation

Martin Bjerregård Pedersen; Xingfei Zhou; Esben Kjaer Unmack Larsen; Uffe Skov Sørensen; Jørgen Kjems; Jens Vinge Nygaard; Jens Randel Nyengaard; Rikke Louise Meyer; Thomas Boesen; Thomas Vorup-Jensen

doi:10.4049/jimmunol.0902214

Curvature of Synthetic and Natural Surfaces is an Important Target Feature in Classical Pathway Complement Activation

Martin Bjerregård Pedersen, Xingfei Zhou, Esben Kjaer Unmack Larsen, Uffe Skov Sørensen, Jørgen Kjems, Jens Vinge Nygaard, Jens Randel Nyengaard, Rikke Louise Meyer, Thomas Boesen, Thomas Vorup-Jensen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

92 Citations (Scopus)

Abstract

The binding of Abs to microbial surfaces followed by complement activation constitutes an important line of defense against infections. In this study, we have investigated the relationship between complement activation and the binding of human IgM Abs to surfaces with different curvatures. IgM Abs to dextran were shown to activate complement potently on dextran-coated particles having a diameter around 250 nm, whereas larger (600 nm) particles were less potent activators. This selectivity regarding particle dimension was also found for complement activation by colloidal substances of microbial origin. Peptidoglycan (PGN) is the major chemical component in the cell wall of Gram-positive bacteria. Fragments of purified PGN with sizes of approximately 100 nm promoted complement activation effectively through the classical pathway. By contrast, larger or smaller fragments of PGN did not activate complement strongly. A careful analysis of PGN fragments released during planctonic growth of Staphylococcus aureus showed that these include curvatures that would permit strong IgM-mediated complement activation, whereas the curvature of intact cells would be less effective for such activation. Consistently, we found that the suspended PGN fragments were strong activators of complement through the classical pathway. We suggest that these fragments act as decoy targets for complement activation, providing protection for S. aureus against the host immune response to infection.

Original language	English
Journal	Journal of Immunology
Volume	184
Issue	4
Pages (from-to)	1931-1945
Number of pages	15
ISSN	0022-1767
DOIs	https://doi.org/10.4049/jimmunol.0902214
Publication status	Published - 2010

Keywords

Antigens, Bacterial
Binding Sites, Antibody
Complement C3
Complement Pathway, Classical
Dextrans
Ferric Compounds
Humans
Immunoglobulin G
Immunoglobulin M
Microscopy, Atomic Force
Nanoparticles
Particle Size
Peptidoglycan
Protein Binding
Staphylococcus aureus
Surface Properties

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10.4049/jimmunol.0902214

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title = "Curvature of Synthetic and Natural Surfaces is an Important Target Feature in Classical Pathway Complement Activation",

abstract = "The binding of Abs to microbial surfaces followed by complement activation constitutes an important line of defense against infections. In this study, we have investigated the relationship between complement activation and the binding of human IgM Abs to surfaces with different curvatures. IgM Abs to dextran were shown to activate complement potently on dextran-coated particles having a diameter around 250 nm, whereas larger (600 nm) particles were less potent activators. This selectivity regarding particle dimension was also found for complement activation by colloidal substances of microbial origin. Peptidoglycan (PGN) is the major chemical component in the cell wall of Gram-positive bacteria. Fragments of purified PGN with sizes of approximately 100 nm promoted complement activation effectively through the classical pathway. By contrast, larger or smaller fragments of PGN did not activate complement strongly. A careful analysis of PGN fragments released during planctonic growth of Staphylococcus aureus showed that these include curvatures that would permit strong IgM-mediated complement activation, whereas the curvature of intact cells would be less effective for such activation. Consistently, we found that the suspended PGN fragments were strong activators of complement through the classical pathway. We suggest that these fragments act as decoy targets for complement activation, providing protection for S. aureus against the host immune response to infection.",

keywords = "Antigens, Bacterial, Binding Sites, Antibody, Complement C3, Complement Pathway, Classical, Dextrans, Ferric Compounds, Humans, Immunoglobulin G, Immunoglobulin M, Microscopy, Atomic Force, Nanoparticles, Particle Size, Peptidoglycan, Protein Binding, Staphylococcus aureus, Surface Properties",

author = "Pedersen, {Martin Bjerreg{\aa}rd} and Xingfei Zhou and Larsen, {Esben Kjaer Unmack} and S{\o}rensen, {Uffe Skov} and J{\o}rgen Kjems and Nygaard, {Jens Vinge} and Nyengaard, {Jens Randel} and Meyer, {Rikke Louise} and Thomas Boesen and Thomas Vorup-Jensen",

year = "2010",

doi = "10.4049/jimmunol.0902214",

language = "English",

volume = "184",

pages = "1931--1945",

journal = "Journal of Immunology",

issn = "0022-1767",

publisher = "American Association of Immunologists",

number = "4",

}

Curvature of Synthetic and Natural Surfaces is an Important Target Feature in Classical Pathway Complement Activation. / Pedersen, Martin Bjerregård; Zhou, Xingfei; Larsen, Esben Kjaer Unmack et al.
In: Journal of Immunology, Vol. 184, No. 4, 2010, p. 1931-1945.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Curvature of Synthetic and Natural Surfaces is an Important Target Feature in Classical Pathway Complement Activation

AU - Pedersen, Martin Bjerregård

AU - Zhou, Xingfei

AU - Larsen, Esben Kjaer Unmack

AU - Sørensen, Uffe Skov

AU - Kjems, Jørgen

AU - Nygaard, Jens Vinge

AU - Nyengaard, Jens Randel

AU - Meyer, Rikke Louise

AU - Boesen, Thomas

AU - Vorup-Jensen, Thomas

PY - 2010

Y1 - 2010

N2 - The binding of Abs to microbial surfaces followed by complement activation constitutes an important line of defense against infections. In this study, we have investigated the relationship between complement activation and the binding of human IgM Abs to surfaces with different curvatures. IgM Abs to dextran were shown to activate complement potently on dextran-coated particles having a diameter around 250 nm, whereas larger (600 nm) particles were less potent activators. This selectivity regarding particle dimension was also found for complement activation by colloidal substances of microbial origin. Peptidoglycan (PGN) is the major chemical component in the cell wall of Gram-positive bacteria. Fragments of purified PGN with sizes of approximately 100 nm promoted complement activation effectively through the classical pathway. By contrast, larger or smaller fragments of PGN did not activate complement strongly. A careful analysis of PGN fragments released during planctonic growth of Staphylococcus aureus showed that these include curvatures that would permit strong IgM-mediated complement activation, whereas the curvature of intact cells would be less effective for such activation. Consistently, we found that the suspended PGN fragments were strong activators of complement through the classical pathway. We suggest that these fragments act as decoy targets for complement activation, providing protection for S. aureus against the host immune response to infection.

AB - The binding of Abs to microbial surfaces followed by complement activation constitutes an important line of defense against infections. In this study, we have investigated the relationship between complement activation and the binding of human IgM Abs to surfaces with different curvatures. IgM Abs to dextran were shown to activate complement potently on dextran-coated particles having a diameter around 250 nm, whereas larger (600 nm) particles were less potent activators. This selectivity regarding particle dimension was also found for complement activation by colloidal substances of microbial origin. Peptidoglycan (PGN) is the major chemical component in the cell wall of Gram-positive bacteria. Fragments of purified PGN with sizes of approximately 100 nm promoted complement activation effectively through the classical pathway. By contrast, larger or smaller fragments of PGN did not activate complement strongly. A careful analysis of PGN fragments released during planctonic growth of Staphylococcus aureus showed that these include curvatures that would permit strong IgM-mediated complement activation, whereas the curvature of intact cells would be less effective for such activation. Consistently, we found that the suspended PGN fragments were strong activators of complement through the classical pathway. We suggest that these fragments act as decoy targets for complement activation, providing protection for S. aureus against the host immune response to infection.

KW - Antigens, Bacterial

KW - Binding Sites, Antibody

KW - Complement C3

KW - Complement Pathway, Classical

KW - Dextrans

KW - Ferric Compounds

KW - Humans

KW - Immunoglobulin G

KW - Immunoglobulin M

KW - Microscopy, Atomic Force

KW - Nanoparticles

KW - Particle Size

KW - Peptidoglycan

KW - Protein Binding

KW - Staphylococcus aureus

KW - Surface Properties

U2 - 10.4049/jimmunol.0902214

DO - 10.4049/jimmunol.0902214

M3 - Journal article

C2 - 20053940

SN - 0022-1767

VL - 184

SP - 1931

EP - 1945

JO - Journal of Immunology

JF - Journal of Immunology

IS - 4

ER -

Curvature of Synthetic and Natural Surfaces is an Important Target Feature in Classical Pathway Complement Activation

Abstract

Keywords

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