Anat Cell Biol.  2015 Dec;48(4):225-234. 10.5115/acb.2015.48.4.225.

Role of mast cell in the late phase of contact hypersensitivity induced by trimellitic anhydride

• Chai OH
• Song CH

• KMID: 2133261
• DOI: http://doi.org/10.5115/acb.2015.48.4.225

Abstract

Mast cells are known as effector cells of IgE-mediated allergic responses, but role of mast cells in contact hypersensitivity (CHS) has been considered controversial. In this study, we investigated role of mast cell in trimellitic anhydride (TMA)-induced CHS. The mice were sensitized to TMA on the back and repeatedly challenged with TMA on the left ear at 1-week intervals. The ear after challenge showed biphasic responses. The repetition of TMA challenge shifted in time course of ear response and enlarged the extent of early and late phase reactions in proportion to the frequency of TMA challenges in C57BL/6 mice. In late phase reaction, peak of ear response by single challenge showed at 24 hours after challenge, but the peak by repeat challenges at 8 hours after the last challenge. Number of mast cells and eosinophils per unit area increased in proportion to frequency of TMA challenges. However, mast cell-deficient WBB6F1/J-Kit(W)/Kit(W-v) mice developed the late phase reaction without the early phase reaction. The repetition of TMA challenge shifted in time course of ear response and enlarged the extent of ear response and the infiltration of eosinophils. The magnitude of these responses observed according to the frequency of the TMA challenge in mast cell-deficient WBB6F1/J-Kit(W)/Kit(W-v) mice was significantly lower than that in C57BL/6 mice. Also TMA elicited mast cell degranulation and histamine release from rat peritoneal mast cells in a concentration-dependent manner. Conclusively, TMA induces the early and late phase reactions in CHS, and mast cells may be required for TMA-induced CHS.

Keyword

Mast cells; Trimellitic anhydride; Contact hypersensitivity; Biphasic response

MeSH Terms

Animals
Dermatitis, Contact*
Ear
Eosinophils
Histamine Release
Mast Cells*
Mice
Rats

Figure

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  Fig. 1 Schematic diagram of the experimental protocol. Mice were sensitized on shaved back skin with 100 µl of 50 mg/ml tissue microarray (TMA) in a 4:1 acetone: olive oil solution (A/O) on day 0 and 50 µl of 12.5 mg/ml TMA in A/O on day 7. On days 14, 21, 28, and 35, each left ear was repeatedly challenged with 20 µl of 2 mg/ml TMA in A/O and each right ear was repeatedly with 20 µl of A/O.

• 

  Fig. 2 (A, B) Ear swelling response on time course following vehicle or tissue microarray (TMA) challenges on the ear of the C57BL/6 mice sensitized on the back skin with TMA. Significant responses were recognized in the vehicle-applied ears compared with the TMA-challenged ears (*P<0.05, ***P<0.001, ###P<0.001).

• 

  Fig. 3 Light micrographs of infiltration of eosinophils on 72 hours after vehicle (A) or one time (B) and four times (C) of the tissue microarray (TMA) challenges on the ear of the C57BL/6 mice sensitized on the back skin with TMA. Congo red stain. Scale bars=10 µm (A-C).

• 

  Fig. 4 Light micrographs of infiltration of mast cells on 72 hours after vehicle (A) or one time (B), and four times (C) of the tissue microarray (TMA) challenges on the ear of the C57BL/6 mice sensitized on the back skin with TMA. Alcian blue stain. Scale bars=10 µm (A-C).

• 

  Fig. 5 Ear swelling response on time course following vehicle or one time (A), two times (B), and four times (C) of tissue microarray (TMA) challenge on the ear of the mast cell-deficient WBB6F1/J-KitW/KitW-v (open circle) and normal (closed circle) mice sensitized on the back skin with TMA. Significant responses were recognized in the TMA-challend ears of mast cell-deficient WBB6F1/J-KitW/KitW-v compared with those of normal mice (**P<0.01, ***P<0.001).

• 

  Fig. 6 Light micrographs of infiltration of eosinophils on 72 hours after vehicle (A) and four times (B) of the tissue microarray (TMA) challenges on the ear of the mast cell-deficient WBB6F1/J-KitW/KitW-v mice sensitized on the back skin with TMA. Congo red stain. Scale bars=10 µm (A, B).

• 

  Fig. 7 Light micrographs of rat peritoneal mast cells with HEPES-Tyrode buffered solution (A) or tissue microarray (TMA) (B). The mast cell in HEPES-Tyrode buffered solution showed clear, smooth outline, spheroidal shape and contained many retractile granules in cytoplasm. After the stimulation with 10 mg/ml TMA, the cell became swollen and had many vacuoles, and extruded granules near cell surface and in the surrounding medium. Scale bars=10 µm (A, B).

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