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Osteopontin is involved in the initiation of cutaneous contact hypersensitivity by inducing Langerhans and dendritic cell migration to lymph nodes.

Weiss JM, Renkl AC, Maier CS, Kimmig M, Liaw L, Ahrens T, Kon S, Maeda M, Hotta H, Uede T, Simon JC - J. Exp. Med. (2001)

Bottom Line: Characterizing OPN function for LC/DC migration we found upregulated OPN expression in hapten sensitized skin and draining lymph nodes.OPN induces chemotactic LC/DC migration, initiates their emigration from the epidermis, and attracts LCs/DCs to draining lymph nodes by interacting with CD44 and alphav integrin.In conclusion, OPN is an important factor in the initiation of CHS by guiding LCs/DCs from skin into lymphatic organs.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University of Freiburg, D-79104 Freiburg, Germany. weiss@haut.ukl.uni-freiburg.de

ABSTRACT
Osteopontin (OPN) is a chemotactic protein that attracts immune cells, to inflammatory sites. The sensitization phase of allergic cutaneous contact hypersensitivity (CHS) requires the migration of Langerhans cells/dendritic cells (LCs/DCs) from skin to draining lymph nodes. Characterizing OPN function for LC/DC migration we found upregulated OPN expression in hapten sensitized skin and draining lymph nodes. OPN induces chemotactic LC/DC migration, initiates their emigration from the epidermis, and attracts LCs/DCs to draining lymph nodes by interacting with CD44 and alphav integrin. Furthermore, OPN-deficient mice have a significantly reduced CHS response that correlates with an impaired ability of OPN-deficient mice to attract LCs/DCs to draining lymph nodes. In conclusion, OPN is an important factor in the initiation of CHS by guiding LCs/DCs from skin into lymphatic organs.

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Related in: MedlinePlus

OPN-induced migration of DCs is dependent on CD44 and the αv integrin subunit on DCs. 106 untreated murine DCs or DCs pretreated with 10 μg/ml of control antibody (Y13–259), anti-CD44 mAbs (IM7), or anti-αv mAb (RMV7) were added to the upper chamber of modified Boyden chambers in the presence or absence of Ca2+/Mg2+. In all assays DCs migrated for 4 h at 37°C. Data is shown as cells/mm2 ± SD of four chambers.
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fig5: OPN-induced migration of DCs is dependent on CD44 and the αv integrin subunit on DCs. 106 untreated murine DCs or DCs pretreated with 10 μg/ml of control antibody (Y13–259), anti-CD44 mAbs (IM7), or anti-αv mAb (RMV7) were added to the upper chamber of modified Boyden chambers in the presence or absence of Ca2+/Mg2+. In all assays DCs migrated for 4 h at 37°C. Data is shown as cells/mm2 ± SD of four chambers.

Mentions: Having identified two putative OPN receptors, CD44 and αvβ3 on DCs, we next sought to determine their functional role for OPN-mediated DC migration. DCs were preincubated with mAbs against αv (RMV7), anti-CD44 (IM7 or KM81), or appropriate control mAb. Chemotaxis-chamber experiments were then performed in the presence or absence of divalent cations (Fig. 5) . In Ca2+/Mg2+ free medium anti-αv integrin mAb did not affect DC migration toward OPN, while anti-CD44 mAb IM7 (Fig. 5) and KM81 (data not shown) inhibited OPN-induced migration. In Ca2+/Mg2+ containing medium, both anti-αv integrin and anti-CD44 mAbs blocked DC migration (Fig. 5). Combination of anti-CD44 and αv mAbs resulted in a complete block of DC migration toward OPN (Fig. 5). Spontaneous chemokinesis or LPS-induced DC migration were not affected by any of the mAbs (data not shown).


Osteopontin is involved in the initiation of cutaneous contact hypersensitivity by inducing Langerhans and dendritic cell migration to lymph nodes.

Weiss JM, Renkl AC, Maier CS, Kimmig M, Liaw L, Ahrens T, Kon S, Maeda M, Hotta H, Uede T, Simon JC - J. Exp. Med. (2001)

OPN-induced migration of DCs is dependent on CD44 and the αv integrin subunit on DCs. 106 untreated murine DCs or DCs pretreated with 10 μg/ml of control antibody (Y13–259), anti-CD44 mAbs (IM7), or anti-αv mAb (RMV7) were added to the upper chamber of modified Boyden chambers in the presence or absence of Ca2+/Mg2+. In all assays DCs migrated for 4 h at 37°C. Data is shown as cells/mm2 ± SD of four chambers.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195976&req=5

fig5: OPN-induced migration of DCs is dependent on CD44 and the αv integrin subunit on DCs. 106 untreated murine DCs or DCs pretreated with 10 μg/ml of control antibody (Y13–259), anti-CD44 mAbs (IM7), or anti-αv mAb (RMV7) were added to the upper chamber of modified Boyden chambers in the presence or absence of Ca2+/Mg2+. In all assays DCs migrated for 4 h at 37°C. Data is shown as cells/mm2 ± SD of four chambers.
Mentions: Having identified two putative OPN receptors, CD44 and αvβ3 on DCs, we next sought to determine their functional role for OPN-mediated DC migration. DCs were preincubated with mAbs against αv (RMV7), anti-CD44 (IM7 or KM81), or appropriate control mAb. Chemotaxis-chamber experiments were then performed in the presence or absence of divalent cations (Fig. 5) . In Ca2+/Mg2+ free medium anti-αv integrin mAb did not affect DC migration toward OPN, while anti-CD44 mAb IM7 (Fig. 5) and KM81 (data not shown) inhibited OPN-induced migration. In Ca2+/Mg2+ containing medium, both anti-αv integrin and anti-CD44 mAbs blocked DC migration (Fig. 5). Combination of anti-CD44 and αv mAbs resulted in a complete block of DC migration toward OPN (Fig. 5). Spontaneous chemokinesis or LPS-induced DC migration were not affected by any of the mAbs (data not shown).

Bottom Line: Characterizing OPN function for LC/DC migration we found upregulated OPN expression in hapten sensitized skin and draining lymph nodes.OPN induces chemotactic LC/DC migration, initiates their emigration from the epidermis, and attracts LCs/DCs to draining lymph nodes by interacting with CD44 and alphav integrin.In conclusion, OPN is an important factor in the initiation of CHS by guiding LCs/DCs from skin into lymphatic organs.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University of Freiburg, D-79104 Freiburg, Germany. weiss@haut.ukl.uni-freiburg.de

ABSTRACT
Osteopontin (OPN) is a chemotactic protein that attracts immune cells, to inflammatory sites. The sensitization phase of allergic cutaneous contact hypersensitivity (CHS) requires the migration of Langerhans cells/dendritic cells (LCs/DCs) from skin to draining lymph nodes. Characterizing OPN function for LC/DC migration we found upregulated OPN expression in hapten sensitized skin and draining lymph nodes. OPN induces chemotactic LC/DC migration, initiates their emigration from the epidermis, and attracts LCs/DCs to draining lymph nodes by interacting with CD44 and alphav integrin. Furthermore, OPN-deficient mice have a significantly reduced CHS response that correlates with an impaired ability of OPN-deficient mice to attract LCs/DCs to draining lymph nodes. In conclusion, OPN is an important factor in the initiation of CHS by guiding LCs/DCs from skin into lymphatic organs.

Show MeSH
Related in: MedlinePlus