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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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OPN induces emigration of LCs from the epidermis which is partially inhibited by mAbs against CD44 and αv. Groups of three mice were left untreated or injected with either PBS, GST control protein (50 μg/ml), or GST-OPN (50 μg/ml in PBS) into the pinnae of ears (A and B). In panel A epidermal sheets were stained by ATPase histochemistry as described in Materials and Methods. Within the epidermis ATPase is specifically expressed by LCs, stained dendritic LCs appear dark brown (bar 18 μm). For mAb blocking experiments, anti-CD44 mAb (IM7), αv (RMV7), or isotype-matched control antibodies (all 10 μg/ml) were added to the volume injected (C). Ears were removed after 48 h, epidermal sheets were prepared and stained for ATPase expression, and LC/mm2 were counted by microscope as described in Materials and Methods. * = statistically significant at P < 0.05, one way analysis of variance (ANOVA), Student-Newmann-Keuls test of four ears. Percent induction was calculated by defining the number of LCs in untreated ears as 0%.
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fig6: OPN induces emigration of LCs from the epidermis which is partially inhibited by mAbs against CD44 and αv. Groups of three mice were left untreated or injected with either PBS, GST control protein (50 μg/ml), or GST-OPN (50 μg/ml in PBS) into the pinnae of ears (A and B). In panel A epidermal sheets were stained by ATPase histochemistry as described in Materials and Methods. Within the epidermis ATPase is specifically expressed by LCs, stained dendritic LCs appear dark brown (bar 18 μm). For mAb blocking experiments, anti-CD44 mAb (IM7), αv (RMV7), or isotype-matched control antibodies (all 10 μg/ml) were added to the volume injected (C). Ears were removed after 48 h, epidermal sheets were prepared and stained for ATPase expression, and LC/mm2 were counted by microscope as described in Materials and Methods. * = statistically significant at P < 0.05, one way analysis of variance (ANOVA), Student-Newmann-Keuls test of four ears. Percent induction was calculated by defining the number of LCs in untreated ears as 0%.

Mentions: Analysis of LC emigration from epidermal sheets is a well-defined system to study skin DC migration in vivo (41). To confirm a functional role of OPN in LC/DC migration in vivo, OPN or appropriate controls were injected into the ear pinnae of mice. After 48 h ears were obtained and LCs within the epidermal sheets were identified by ATPase staining (34; Fig. 6 A). The number of LCs remaining within the epidermis was quantified by microscope. In OPN-injected ears, up to 50% of LC had left the epidermis after 48 h (Fig. 6, A and B) indicating that OPN strongly induced DC migration from the epidermis in vivo. In accordance with the in vitro migration experiments this effect could be partially blocked by mAbs against CD44 and αv (Fig. 6 C). While anti-CD44 mAb injected simultaneously with OPN almost completely blocked OPN stimulated LC emigration from the skin, the anti-αv antibody had an inhibitory effect of up to 50%.


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 induces emigration of LCs from the epidermis which is partially inhibited by mAbs against CD44 and αv. Groups of three mice were left untreated or injected with either PBS, GST control protein (50 μg/ml), or GST-OPN (50 μg/ml in PBS) into the pinnae of ears (A and B). In panel A epidermal sheets were stained by ATPase histochemistry as described in Materials and Methods. Within the epidermis ATPase is specifically expressed by LCs, stained dendritic LCs appear dark brown (bar 18 μm). For mAb blocking experiments, anti-CD44 mAb (IM7), αv (RMV7), or isotype-matched control antibodies (all 10 μg/ml) were added to the volume injected (C). Ears were removed after 48 h, epidermal sheets were prepared and stained for ATPase expression, and LC/mm2 were counted by microscope as described in Materials and Methods. * = statistically significant at P < 0.05, one way analysis of variance (ANOVA), Student-Newmann-Keuls test of four ears. Percent induction was calculated by defining the number of LCs in untreated ears as 0%.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2195976&req=5

fig6: OPN induces emigration of LCs from the epidermis which is partially inhibited by mAbs against CD44 and αv. Groups of three mice were left untreated or injected with either PBS, GST control protein (50 μg/ml), or GST-OPN (50 μg/ml in PBS) into the pinnae of ears (A and B). In panel A epidermal sheets were stained by ATPase histochemistry as described in Materials and Methods. Within the epidermis ATPase is specifically expressed by LCs, stained dendritic LCs appear dark brown (bar 18 μm). For mAb blocking experiments, anti-CD44 mAb (IM7), αv (RMV7), or isotype-matched control antibodies (all 10 μg/ml) were added to the volume injected (C). Ears were removed after 48 h, epidermal sheets were prepared and stained for ATPase expression, and LC/mm2 were counted by microscope as described in Materials and Methods. * = statistically significant at P < 0.05, one way analysis of variance (ANOVA), Student-Newmann-Keuls test of four ears. Percent induction was calculated by defining the number of LCs in untreated ears as 0%.
Mentions: Analysis of LC emigration from epidermal sheets is a well-defined system to study skin DC migration in vivo (41). To confirm a functional role of OPN in LC/DC migration in vivo, OPN or appropriate controls were injected into the ear pinnae of mice. After 48 h ears were obtained and LCs within the epidermal sheets were identified by ATPase staining (34; Fig. 6 A). The number of LCs remaining within the epidermis was quantified by microscope. In OPN-injected ears, up to 50% of LC had left the epidermis after 48 h (Fig. 6, A and B) indicating that OPN strongly induced DC migration from the epidermis in vivo. In accordance with the in vitro migration experiments this effect could be partially blocked by mAbs against CD44 and αv (Fig. 6 C). While anti-CD44 mAb injected simultaneously with OPN almost completely blocked OPN stimulated LC emigration from the skin, the anti-αv antibody had an inhibitory effect of up to 50%.

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