Rheins L A, Nordlund J J
J Immunol. 1986 Feb 1;136(3):867-76.
The epidermis on the backs or ears of DBA/2 mice treated for 7 days with a 20% concentration of monobenzyl ether of hydroquinone (MBEH) had a significantly greater population density of ATPase- and Ia-positive cells compared with control mice treated with diluent. There was no decrease or increase in ATPase- or Ia-positive cells at sites distal from the treated tissue. This increase in population density of Langerhans cells was associated with a significant increase in functional afferent immune reactivity measured by allergic contact hypersensitivity. We also found evidence for enhanced efferent immune reactivity. Animals treated on the ears for 7 days with MBEH were sensitized to DNFB on untreated back. MBEH treated ears with more Ia-positive Langerhans cells demonstrated a threefold greater increase in swelling after the DNFB challenge than the control mice. Results of other studies suggest that the afferent and efferent enhanced immune reactivity produced by MBEH are local effects. We postulated that MBEH produced its effects by activating the oxidation of arachidonic acid (AA) to prostaglandins. To test this, we applied AA to mouse skin. AA has a biphasic effect on epidermal Langerhans cells: in low doses it increases their number; in high amounts it decreases the number of identifiable cells with either the Ia or the ATPase technique. An increased population density of identifiable epidermal Langerhans cells induced with AA was correlated with an increase in afferent and efferent immune reactivity. In contrast, reduction of Langerhans cells with larger amounts of AA suppress the afferent and efferent limb of the immune response. DNFB applied to skin with decreased Langerhans cell density from AA induced a state that mimics immune tolerance. The findings are significant because we report the only method to either increase or decrease the population density of Langerhans cells: and to modulate up or down the afferent or efferent limbs of the cutaneous immune response. Our results also suggest that the Langerhans cell may be involved in the efferent limb of the immune efferent response. These effects may be modulated in part by products of AA metabolism.
用20%浓度的对苯二酚单苄醚（MBEH）处理7天的DBA/2小鼠背部或耳部的表皮，与用稀释剂处理的对照小鼠相比，ATP酶和Ia阳性细胞的群体密度显著更高。在远离处理组织的部位，ATP酶或Ia阳性细胞没有减少或增加。朗格汉斯细胞群体密度的这种增加与通过过敏性接触超敏反应测量的功能性传入免疫反应性的显著增加相关。我们还发现了传出免疫反应性增强的证据。用MBEH处理耳部7天的动物对未处理背部的二硝基氟苯（DNFB）致敏。具有更多Ia阳性朗格汉斯细胞的MBEH处理耳部在DNFB激发后肿胀增加幅度比对照小鼠大三倍。其他研究结果表明，MBEH产生的传入和传出增强免疫反应是局部效应。我们推测MBEH通过激活花生四烯酸（AA）氧化为前列腺素而产生其作用。为了验证这一点，我们将AA应用于小鼠皮肤。AA对表皮朗格汉斯细胞有双相作用：低剂量时增加其数量；高剂量时用Ia或ATP酶技术可减少可识别细胞的数量。由AA诱导的可识别表皮朗格汉斯细胞群体密度增加与传入和传出免疫反应性增加相关。相反，用大量AA减少朗格汉斯细胞会抑制免疫反应的传入和传出分支。将DNFB应用于因AA导致朗格汉斯细胞密度降低的皮肤会诱导出一种模拟免疫耐受的状态。这些发现意义重大，因为我们报告了增加或减少朗格汉斯细胞群体密度以及上调或下调皮肤免疫反应的传入或传出分支的唯一方法。我们的结果还表明，朗格汉斯细胞可能参与免疫传出反应的传出分支。这些效应可能部分由AA代谢产物调节。
