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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

DCs migrate toward OPN in a dose-dependent manner in the presence or absence of divalent cations. Mouse DC (106 cells) were placed into the upper chambers of modified Boyden chambers as described in Materials and Methods. GST control protein (2 μg/ml) or the indicated concentrations of GST-OPN were added to the lower chamber. Assays were performed in HBSS without Ca2+/Mg++ (A) or with Ca2+/Mg++ (B). Data are shown as cells/mm2 ± SD of four chambers.
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fig3: DCs migrate toward OPN in a dose-dependent manner in the presence or absence of divalent cations. Mouse DC (106 cells) were placed into the upper chambers of modified Boyden chambers as described in Materials and Methods. GST control protein (2 μg/ml) or the indicated concentrations of GST-OPN were added to the lower chamber. Assays were performed in HBSS without Ca2+/Mg++ (A) or with Ca2+/Mg++ (B). Data are shown as cells/mm2 ± SD of four chambers.

Mentions: Having demonstrated that OPN is expressed in skin and in lymph nodes draining that skin site during the sensitization phase of CHS we investigated whether OPN could function as a chemoattractant for murine LCs/DCs. Two putative OPN receptors CD44 and αvβ3 are functionally involved in OPN-mediated cell migration (22, 24). While αvβ3-mediated migration requires divalent cations, CD44-mediated OPN effects are Ca2+/Mg2+ independent (22, 23, 24). We used recombinant GST-OPN to assess DC migration toward OPN in microchamber migration assays in the presence or absence of Ca2+/Mg2+. Addition of recombinant GST-OPN to the lower chamber induced DC migration in a dose-dependent manner in both settings. However, in the presence of Ca2+/Mg2+, up to 30% more DCs migrated toward OPN (Fig. 3) . DCs migrated toward OPN in a manner resembling chemotaxis rather than chemokinesis because increasing concentrations of OPN in the upper chamber inhibited DC migration toward OPN (Table I). These findings indicate that OPN stimulates DC migration and that both Ca2+/Mg2+-dependent and -independent receptors are involved in DC migration toward OPN.


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)

DCs migrate toward OPN in a dose-dependent manner in the presence or absence of divalent cations. Mouse DC (106 cells) were placed into the upper chambers of modified Boyden chambers as described in Materials and Methods. GST control protein (2 μg/ml) or the indicated concentrations of GST-OPN were added to the lower chamber. Assays were performed in HBSS without Ca2+/Mg++ (A) or with Ca2+/Mg++ (B). Data are shown as cells/mm2 ± SD of four chambers.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: DCs migrate toward OPN in a dose-dependent manner in the presence or absence of divalent cations. Mouse DC (106 cells) were placed into the upper chambers of modified Boyden chambers as described in Materials and Methods. GST control protein (2 μg/ml) or the indicated concentrations of GST-OPN were added to the lower chamber. Assays were performed in HBSS without Ca2+/Mg++ (A) or with Ca2+/Mg++ (B). Data are shown as cells/mm2 ± SD of four chambers.
Mentions: Having demonstrated that OPN is expressed in skin and in lymph nodes draining that skin site during the sensitization phase of CHS we investigated whether OPN could function as a chemoattractant for murine LCs/DCs. Two putative OPN receptors CD44 and αvβ3 are functionally involved in OPN-mediated cell migration (22, 24). While αvβ3-mediated migration requires divalent cations, CD44-mediated OPN effects are Ca2+/Mg2+ independent (22, 23, 24). We used recombinant GST-OPN to assess DC migration toward OPN in microchamber migration assays in the presence or absence of Ca2+/Mg2+. Addition of recombinant GST-OPN to the lower chamber induced DC migration in a dose-dependent manner in both settings. However, in the presence of Ca2+/Mg2+, up to 30% more DCs migrated toward OPN (Fig. 3) . DCs migrated toward OPN in a manner resembling chemotaxis rather than chemokinesis because increasing concentrations of OPN in the upper chamber inhibited DC migration toward OPN (Table I). These findings indicate that OPN stimulates DC migration and that both Ca2+/Mg2+-dependent and -independent receptors are involved in DC migration toward OPN.

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