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Osteopontin enhances phagocytosis through a novel osteopontin receptor, the alphaXbeta2 integrin

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Osteopontin enhances phagocytosis through a novel osteopontin receptor, the alphaXbeta2 integrin. / Schack, Lotte; Stapulionis, Romualdas; Christensen, Brian; Kofod-Olsen, Emil; Sørensen, Uffe B. Skov; Vorup-Jensen, Thomas; Sørensen, Esben S; Höllsberg, Per.

I: Journal of Immunology, Bind 182, Nr. 11, 2009, s. 6943-50.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{cdb19d60558e11de8dc9000ea68e967b,
title = "Osteopontin enhances phagocytosis through a novel osteopontin receptor, the alphaXbeta2 integrin",
abstract = "Osteopontin (OPN) is a cytokine with multiple functions, including immune defense mechanisms against invading microorganisms. OPN-deficient mice are impaired in clearing intracellular pathogens, suggesting an important role of OPN during phagocytosis, but it remains to be defined how OPN may enhance this innate immune process. Here, we demonstrate that OPN binds to monocytes, but not resting T cells, NK cells, or B cells, and mediates chemoattraction of IL-1-activated human monocytes. Moreover, OPN binds in a specific manner to all known serotypes of the two bacterial species Streptococcus agalactiae and Staphylococcus aureus and opsonizes these bacteria for phagocytosis. We identify the integrin alpha(X)beta(2) (CD11c/CD18), which is highly expressed on the cell surface of monocytes, as a novel OPN receptor. To eliminate the contribution from other molecular interactions between the bacteria and the phagocyte, we show that OPN-coated synthetic beads are phagocytosed in an alpha(X)beta(2) integrin-dependent manner. The ligand recognition does not involve the RGD motif previously reported to support binding of OPN to integrins. Taken together, these data identify the alpha(X)beta(2) integrin as a novel OPN receptor that is required for OPN-mediated phagocytosis, thereby elucidating an important mechanism of an innate immune function of OPN.",
author = "Lotte Schack and Romualdas Stapulionis and Brian Christensen and Emil Kofod-Olsen and S{\o}rensen, {Uffe B. Skov} and Thomas Vorup-Jensen and S{\o}rensen, {Esben S} and Per H{\"o}llsberg",
year = "2009",
doi = "10.4049/jimmunol.0900065",
language = "English",
volume = "182",
pages = "6943--50",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "11",

}

RIS

TY - JOUR

T1 - Osteopontin enhances phagocytosis through a novel osteopontin receptor, the alphaXbeta2 integrin

AU - Schack, Lotte

AU - Stapulionis, Romualdas

AU - Christensen, Brian

AU - Kofod-Olsen, Emil

AU - Sørensen, Uffe B. Skov

AU - Vorup-Jensen, Thomas

AU - Sørensen, Esben S

AU - Höllsberg, Per

PY - 2009

Y1 - 2009

N2 - Osteopontin (OPN) is a cytokine with multiple functions, including immune defense mechanisms against invading microorganisms. OPN-deficient mice are impaired in clearing intracellular pathogens, suggesting an important role of OPN during phagocytosis, but it remains to be defined how OPN may enhance this innate immune process. Here, we demonstrate that OPN binds to monocytes, but not resting T cells, NK cells, or B cells, and mediates chemoattraction of IL-1-activated human monocytes. Moreover, OPN binds in a specific manner to all known serotypes of the two bacterial species Streptococcus agalactiae and Staphylococcus aureus and opsonizes these bacteria for phagocytosis. We identify the integrin alpha(X)beta(2) (CD11c/CD18), which is highly expressed on the cell surface of monocytes, as a novel OPN receptor. To eliminate the contribution from other molecular interactions between the bacteria and the phagocyte, we show that OPN-coated synthetic beads are phagocytosed in an alpha(X)beta(2) integrin-dependent manner. The ligand recognition does not involve the RGD motif previously reported to support binding of OPN to integrins. Taken together, these data identify the alpha(X)beta(2) integrin as a novel OPN receptor that is required for OPN-mediated phagocytosis, thereby elucidating an important mechanism of an innate immune function of OPN.

AB - Osteopontin (OPN) is a cytokine with multiple functions, including immune defense mechanisms against invading microorganisms. OPN-deficient mice are impaired in clearing intracellular pathogens, suggesting an important role of OPN during phagocytosis, but it remains to be defined how OPN may enhance this innate immune process. Here, we demonstrate that OPN binds to monocytes, but not resting T cells, NK cells, or B cells, and mediates chemoattraction of IL-1-activated human monocytes. Moreover, OPN binds in a specific manner to all known serotypes of the two bacterial species Streptococcus agalactiae and Staphylococcus aureus and opsonizes these bacteria for phagocytosis. We identify the integrin alpha(X)beta(2) (CD11c/CD18), which is highly expressed on the cell surface of monocytes, as a novel OPN receptor. To eliminate the contribution from other molecular interactions between the bacteria and the phagocyte, we show that OPN-coated synthetic beads are phagocytosed in an alpha(X)beta(2) integrin-dependent manner. The ligand recognition does not involve the RGD motif previously reported to support binding of OPN to integrins. Taken together, these data identify the alpha(X)beta(2) integrin as a novel OPN receptor that is required for OPN-mediated phagocytosis, thereby elucidating an important mechanism of an innate immune function of OPN.

U2 - 10.4049/jimmunol.0900065

DO - 10.4049/jimmunol.0900065

M3 - Journal article

C2 - 19454691

VL - 182

SP - 6943

EP - 6950

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 11

ER -