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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

αvβ3 expression is upregulated during DC maturation. Murine DCs were generated from bone marrow precursors, purified by density gradient as described in Materials and Methods, and stained for FACS® analysis with mAbs against (A) αv (CD51), (B) β3 (CD61, mAb) integrin, or (C) pan CD44 mAb. DC were harvested on days 6, 7, and 8 of DC culture.
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fig4: αvβ3 expression is upregulated during DC maturation. Murine DCs were generated from bone marrow precursors, purified by density gradient as described in Materials and Methods, and stained for FACS® analysis with mAbs against (A) αv (CD51), (B) β3 (CD61, mAb) integrin, or (C) pan CD44 mAb. DC were harvested on days 6, 7, and 8 of DC culture.

Mentions: Our chemotaxis experiments indicated that OPN-induced DC migration can be mediated by Ca2+/Mg2+-dependent and -independent mechanisms. CD44 has been characterized as a migration-mediating OPN receptor acting in the absence of Ca2+/Mg2+ (23). Having previously demonstrated the importance of CD44 for DC function during the sensitization phase of CHS (25) we now investigated the expression of the Ca2+/Mg2+-dependent OPN receptor αvβ3 on DCs. DCs were generated from bone marrow culture and analyzed by FACS® (DC purity >80% by definition of high expression of Iab, CD11c, B7–1, and B7–2 in FACS® analysis [30]). Immature DCs from day 6 bone marrow-DC cultures expressed both αvβ3 (CD51/CD61; Fig. 4, A and B) and CD44 (Fig. 4 C). Upon maturation in bone marrow-DC cultures αvβ3 expression was gradually upregulated from day 6 to 8 while CD44 was consistently expressed (Fig. 4, A–C). Taken together these results support the notion that the two OPN receptors αvβ3 and CD44 are expressed on murine DCs.


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)

αvβ3 expression is upregulated during DC maturation. Murine DCs were generated from bone marrow precursors, purified by density gradient as described in Materials and Methods, and stained for FACS® analysis with mAbs against (A) αv (CD51), (B) β3 (CD61, mAb) integrin, or (C) pan CD44 mAb. DC were harvested on days 6, 7, and 8 of DC culture.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: αvβ3 expression is upregulated during DC maturation. Murine DCs were generated from bone marrow precursors, purified by density gradient as described in Materials and Methods, and stained for FACS® analysis with mAbs against (A) αv (CD51), (B) β3 (CD61, mAb) integrin, or (C) pan CD44 mAb. DC were harvested on days 6, 7, and 8 of DC culture.
Mentions: Our chemotaxis experiments indicated that OPN-induced DC migration can be mediated by Ca2+/Mg2+-dependent and -independent mechanisms. CD44 has been characterized as a migration-mediating OPN receptor acting in the absence of Ca2+/Mg2+ (23). Having previously demonstrated the importance of CD44 for DC function during the sensitization phase of CHS (25) we now investigated the expression of the Ca2+/Mg2+-dependent OPN receptor αvβ3 on DCs. DCs were generated from bone marrow culture and analyzed by FACS® (DC purity >80% by definition of high expression of Iab, CD11c, B7–1, and B7–2 in FACS® analysis [30]). Immature DCs from day 6 bone marrow-DC cultures expressed both αvβ3 (CD51/CD61; Fig. 4, A and B) and CD44 (Fig. 4 C). Upon maturation in bone marrow-DC cultures αvβ3 expression was gradually upregulated from day 6 to 8 while CD44 was consistently expressed (Fig. 4, A–C). Taken together these results support the notion that the two OPN receptors αvβ3 and CD44 are expressed on murine DCs.

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