Establishment of murine model of eosinophil-infiltrating drug photoallergy and elucidation of its immunological mechanism

我们用具有代表性的光敏药物氟喹酮(AQ)建立了嗜酸性粒细胞浸润型药物光敏反应的小鼠模型。AKR/J小鼠经腹腔注射致敏。氟喹诺酮溶液注射和UVA照射剃须腹部。致敏过程重复2-12次(每周两次)，最后一次免疫后3天，用S.C.注射AQ溶液，并用UVA照射同一部位。接受超过10次致敏的小鼠在受挑战的部位表现出大量的嗜酸性粒细胞和淋巴细胞的渗透。这种反应是AQ光抗原特异性的，AKR/J小鼠是这种敏感性的高反应性品系。用5-8×10~(-7)免疫淋巴和脾细胞成功地将敏感性转移到幼鼠体内。由于1×10~(-7)的CD_4~(2+)细胞单独引起高水平的敏感性反应，而其他淋巴细胞群的加入并不能增强这种反应，因此，CD_4~+T细胞是导致这种敏感性的原因。免疫淋巴结细胞培养上清液中IL-4水平高于幼鼠，而干扰素-g水平低于幼鼠。AQ光激发部位皮肤高表达嗜酸性粒细胞趋化因子CCL24/eoaxin-2。提示嗜酸性药物光敏反应是由致敏的Th2细胞和局部产生的嗜酸性粒细胞趋化因子引起的。该模型可用于探讨嗜酸性粒细胞渗入光敏的机制。

We established a murine model of the eosinophil-infiltrating type of drug photoallergy by using afloqualone (AQ), a representative photosensitive drug. AKR/J mice were sensitized by an i.p. injection of afloqualone solution and irradiation of shaved abdomen with UVA. This sensitization procedure was repeated 2-12 times (twice a week), and 3 days after the last immunization, mice were challenged by an s.c. injection of AQ solution and irradiation of the same site with UVA. Mice receiving more than 10 times of sensitization exhibited a massive infiltrate of eosinophils and lymphocytes at the challenged site. This reaction was AQ photoantigen-specific, and AKR/J mice were a high responder strain of this sensitivity. The sensitivity was successfully transferred with 5-8x10^7 immune lymph node and spleen cells into naive mice. CD4^+ T cells were responsible for this sensitivity, since 1x10^7 CD4^+ cells alone induced a high level of sensitivity reaction and the addition of other lymphocyte populations did not enhance the reaction. Culture supernatants from immune lymph node cells contained a higher level of IL-4 and a lower level of interferon-g than those from naive mice. Finally, the skin of AQ-photochallenged site exhibited high expression of CCL24/eotaxin-2, a chemokine for eosinophils. It is suggested that eosinophilic drug photoallergy is medated by sensitized Th2 cells and locally produced eosinophil-attracting chemokines. This model is useful for exploring the mechanism of eosinophil-infiltrating photosensitivity.