Immunoreactive vasoactive intestinal peptide contributes to the immunosuppressive activity of normal aqueous humor.

Immunoreactive vasoactive intestinal peptide contributes to the immunosuppressive activity of normal aqueous humor.
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DOI:
10.4049/jimmunol.153.3.1080
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发表时间:
1994-08
影响因子:
4.4
通讯作者:
Andrew W. Taylor;J. Streilein;Scott W. Cousins
Andrew W. Taylor;J. Streilein;Scott W. Cousins
中科院分区:
医学2区
文献类型:
--
作者:
Andrew W. Taylor;J. Streilein;Scott W. Cousins

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眼睛的正常前房(AC)内的免疫介导的炎症的抑制部分是由在房水(AqH)(填充AC的流体)中发现的免疫抑制细胞因子主动抑制效应T细胞活性的结果。在低分子量乳腺癌中发现了免疫抑制因子。AqH部分(< 5 kDa),包括神经肽α-黑素细胞刺激激素(α-MSH)。在寻求其他因素,我们现在报告,神经肽血管活性肠肽(VIP)也存在于正常AqH。VIP免疫反应性在正常兔眼中发现,浓度为12 +/- 1 nM。在这个眼内浓度,VIP抑制银刺激的淋巴结细胞(LNC)增殖和IFN-γ的生产在体外。虽然LNC增殖的抑制不能被低分子量VIP的吸收所中和。对于AqH级分,VIP的去除确实中和了该AqH级分对IFN-γ产生的抑制。从AqH的该部分吸收VIP和α-MSH两者允许由Ag刺激的LNC产生IFN-γ,这与单独吸收VIP没有不同。低分子量吸收α-MSH和VIP的AqH部分失去了抑制迟发型超敏反应的局部过继转移的能力。提示VIP是AqH中一种重要的免疫抑制神经肽。神经肽在眼免疫赦免和眼内免疫抑制微环境的建立中起重要作用。
Suppression of immune-mediated inflammation within the normal anterior chamber (AC) of the eye is in part the result of active suppression of effector T cell activities by immunosuppressive cytokines found in aqueous humor (AqH), the fluid filling the AC. There are immunosuppressive factors found in the low m.w. fraction (< 5 kDa) of AqH, including the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH). In seeking other factors, we now report that the neuropeptide vasoactive intestinal peptide (VIP) is also present in normal AqH. VIP immunoreactivity was found in normal rabbit eyes at a concentration of 12 +/- 1 nM. At this intraocular concentration, VIP suppressed Ag-stimulated lymph node cell (LNC) proliferation and IFN-gamma production in vitro. Although suppression of LNC proliferation was not neutralized by absorption of VIP from the low m.w. fraction of AqH, removal of VIP did neutralize suppression of IFN-gamma production by this fraction of AqH. Absorption of both VIP and alpha-MSH from this fraction of AqH permitted production of IFN-gamma by Ag-stimulated LNC that was no different than absorbing VIP alone. The low m.w. fraction of AqH absorbed of either alpha-MSH and VIP lost its ability to suppress local adoptive transfer of delayed-type hypersensitivity. The results suggest that VIP is an important immunosuppressive neuropeptide in AqH. Neuropeptides play an important role in ocular immune privilege and creation of an intraocular immunosuppressive microenvironment.