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Natural killer cells in inflammatory lesions and transplanted tumors in mouse skin
Abstract:
The mode of natural killer (NK) cell migration to the sites of inflammation and transplanted tumors was investigated by using dry ice for physical irritation and 1-fluoro-2,4 dinitrobenzene (DNFB) for chemical irritation in mouse ear. In experiments with transplanted tumors, NK cell sensitive tumor cells (RL male 1) and insensitive tumor cells (p815) were transplanted into the ears of C3H and BALB/c mice, respectively. Employing a polyclonal rabbit antiserum against asialoGM1 (GA1), and a monoclonal rat antiserum against Thy-1 in an immunohistochemical double-staining technique, we enumerated the number of Thy-1-positive and asialoGM1-positive (Thy-1+ GA1+) cells and Thy-1-negative and asialoGM1-positive (Thy-1-GA1+) cells at various times of irritation. Following physical irritation, Thy-1-GA1+ cells (108.8 +/- 4.5/mm2 at 24 h and 71.2 +/- 3.8/mm2 at 48 h) were found in the epidermis, whereas Thy-1+GA1+ cells were not found. In delayed-type skin reaction by DNFB, Thy-1-GA1+ cells (87.1 +/- 5.8/mm2 at 24 h and 60.7 +/- 2.9/mm2 at 48 h) and Thy-1+GA1+ cells (26.4 +/- 3.6/mm2 at 24 h and 15.3 +/- 4.3/mm2 at 48 h) were found in the dermis. Since it was reported by previous investigators that Thy-1+GA1+ cells are NK cells, we assumed that NK cells infiltrated nonspecifically in the dermis in delayed-type skin reaction by DNFB. In the tumor transplant experiments, the GA1+ cells were found near both types of tumors, but they were in contact with RL male 1 and not with p815. Because it was reported that GA1+ monocytes do not have cytotoxicity against tumor cells, our findings suggest that GA1+ cells migrate nonspecifically to the sites of inflammation, and that the NK cells among them may make direct contact with the tumor cells when they encounter NK cell sensitive tumors.
Insights
Natural killer (NK) cell migration was studied using physical and chemical irritation in mice. NK cells infiltrate tissues nonspecifically, but contact sensitive tumor cells directly.
Area of Science:
- Immunology
- Cell Biology
- Dermatology
Background:
- Natural killer (NK) cells are crucial for innate immunity, mediating tumor surveillance and defense against infections.
- Understanding NK cell migration patterns is essential for developing targeted immunotherapies for cancer and inflammatory diseases.
Purpose of the Study:
- To investigate the migration patterns of natural killer (NK) cells to sites of inflammation and transplanted tumors in a mouse model.
- To differentiate between NK cell migration in response to physical/chemical irritation versus tumor cell presence.
Main Methods:
- Utilized dry ice for physical irritation and 1-fluoro-2,4 dinitrobenzene (DNFB) for chemical irritation in mouse ears.
- Transplanted NK-sensitive (RL male 1) and NK-insensitive (p815) tumor cells into mouse ears.
- Employed immunohistochemical double-staining with anti-asialoGM1 (GA1) and anti-Thy-1 antisera to identify and enumerate cell populations.
Main Results:
- Following physical irritation, Thy-1-negative GA1+ cells (likely innate immune cells) were abundant in the epidermis, while Thy-1-positive GA1+ cells (identified as NK cells) were absent.
- In DNFB-induced delayed-type skin reactions, both Thy-1-GA1+ and Thy-1+GA1+ cells were found in the dermis, suggesting non-specific infiltration of NK cells.
- GA1+ cells were observed near both tumor types, but direct contact was only made with NK-sensitive RL male 1 tumor cells, not with p815 cells.
Conclusions:
- GA1+ cells, including NK cells, migrate non-specifically to inflammatory sites.
- NK cells selectively interact with NK-sensitive tumor cells upon encountering them at the tumor site.
- These findings provide insights into NK cell trafficking and tumor immunosurveillance mechanisms.