Sano Yoshifumi, Gomez F Enrique, Hermsen Joshua L, Kang Woodae, Lan Jinggang, Maeshima Yoshinori, Kudsk Kenneth A
Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA.
J Surg Res. 2008 Oct;149(2):236-42. doi: 10.1016/j.jss.2007.12.790. Epub 2008 Jan 29.
Secretory immunoglobulin A (IgA) prevents pathogen adherence at mucosal surfaces to prevent infection. Polymeric immunoglobulin receptor (pIgR), located on the basolateral surface of mucosal cells, binds dimeric IgA produced by B cells with the cooperation of T cells in the lamina propria. This IgA-pIgR complex is transported apically, where it is exocytosed as secretory IgA to the mucosal surface. Our prior work shows that parenteral nutrition (PN) impairs both airway and small intestine mucosal immunity by reducing T and B cells and IgA levels. This work examines intestinal and respiratory tissue-specific pIgR responses to PN.
Cannulated male Institute of Cancer Research mice were randomized to Chow (n = 10) or PN (n = 10). After 5 days, animals were sacrificed and lavages obtained from the small intestine, lung (BAL = bronchoalveolar lavage), and nasal airways (NAL). Small intestine, lung, and nasal passage tissues were also collected. Lavage and tissue homogenate IgA levels were quantified by enzyme-linked immunosorbent assay and pIgR by Western blot.
PN group SIL and NAL IgA levels dropped significantly compared with Chow. PN significantly reduced pIgR levels in the SI while no pIgR change was noted in nasal passages and lung pIgR actually increased with PN. Tissue homogenate IgA levels did not change with PN in the SI while levels in the nasal passage and lung decreased.
PN impairs airway mucosal immunity by reduction in IgA available for transport rather than via a reduction in pIgR levels. In the small intestine, diminished pIgR is implicated in the deterioration of antibody-mediated mucosal immunity.
分泌型免疫球蛋白A(IgA)可防止病原体在黏膜表面黏附,从而预防感染。位于黏膜细胞基底外侧表面的多聚免疫球蛋白受体(pIgR),在固有层T细胞的协同作用下,与B细胞产生的二聚体IgA结合。这种IgA-pIgR复合物被转运至顶端,在此处作为分泌型IgA被胞吐到黏膜表面。我们之前的研究表明,肠外营养(PN)通过降低T细胞、B细胞和IgA水平,损害气道和小肠黏膜免疫。本研究旨在探讨肠道和呼吸道组织特异性pIgR对PN的反应。
将插管的雄性癌症研究所小鼠随机分为正常饮食组(n = 10)和PN组(n = 10)。5天后,处死动物,从小肠、肺(支气管肺泡灌洗)和鼻气道(鼻腔灌洗)获取灌洗液。同时收集小肠、肺和鼻道组织。通过酶联免疫吸附测定法对灌洗液和组织匀浆中的IgA水平进行定量,通过蛋白质免疫印迹法对pIgR进行定量。
与正常饮食组相比,PN组小肠灌洗液(SIL)和鼻腔灌洗液(NAL)中的IgA水平显著下降。PN显著降低了小肠中pIgR的水平,而鼻腔和肺中的pIgR水平未发生变化,实际上肺中的pIgR水平在PN作用下有所升高。小肠组织匀浆中的IgA水平在PN作用下未发生变化,而鼻腔和肺中的水平下降。
PN通过减少可用于转运的IgA来损害气道黏膜免疫,而非通过降低pIgR水平。在小肠中,pIgR减少与抗体介导的黏膜免疫恶化有关。