Intravital Imaging of Dynamic Behaviors of Leukocytes in UVB-induced Skin Inflammation

Ultraviolet B (UVB) irradiation diminishes surface densities of Langerhans cells (LCs) in the epidermis of the skin. Other leukocytes, such as neutrophils and macrophages, are recruited to the irradiated sites due to chemo-attracting factors released from the altered microenvironment. However, there is little evidence directly demonstrating the behavior of LCs as well as other leukocytes in response to UVB radiation, and it is also unknown whether cellular interaction occurs during skin inflammation. In the present study, we developed a direct visualization system to observe the dynamic behaviors of both LCs and neutrophils responding to 3000J/m2 UVB in the skin. Using intravital confocal microscopy and genetically manipulated transgenic mice, we have found that neutrophils are recruited to inflammatory sites immediately after UVB irradiation. Skin-infiltrating neutrophils can interact with LCs upon activation and can last for several hours. Twenty-four hours after irradiation, LCs migrated to deeper skin layers, resulting in a 30% reduction of LC number in the epidermal compartment, whereas the number of recruited neutrophils increased over time. LCs completely disappeared from the epidermis 4 days after UVB treatment. Depletion of neutrophils by anti-Ly6G monoclonal antibody (mAb) administration did not affect LCs migration in response to the same UVB radiation, but rather promoted LC precursors’ repopulation to the epidermis after UVB treatment. In addition, depletion of neutrophils greatly diminished the magnitude of UVB-induced ear swelling, suggesting that neutrophils are crucial for UVB induced skin inflammation. Not only do our data unveil the behavior and cell-cell interaction of LCs and neutrophils upon UVB irradiation, they also indicate for the first time that neutrophils play an important role in LC repopulation.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

College of Medicine

Grantor dc:publisher

University of Toledo Health Science Campus

Year dc:date

2013

Author dc:creator

• Lu, Ran

Contributors dc:contributor

• Takashima, Akira

• Immunology
• Intravital imaging
• UVB
• Skin inflammation

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=mco1357227508

OAI identifier oai:identifier

oai:etd.ohiolink.edu:mco1357227508