Gut mucosal injury in neonates is marked by macrophage infiltration in contrast to pleomorphic infiltrates in adult: evidence from an animal model
Gut mucosal injury in neonates is marked by macrophage infiltration in contrast to pleomorphic infiltrates in adult: evidence from an animal model
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DOI：
10.1152/ajpgi.00016.2012
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发表时间：
2012-07-01
影响因子：
4.5
通讯作者：
Maheshwari, Akhil
中科院分区：
文献类型：
--
作者：
MohanKumar, Krishnan;Kaza, Niroop;Maheshwari, Akhil
Mohankumar K，Kaza N，Jagadeeswaran R，Garzon SA，Bansal A，Kurundkar AR，Namchivayam K，Remon JI，Bandesalli CR，冯X，Weitkamp J-H，Mahehwari A.新生儿的肠道粘膜损伤以巨噬细胞浸润为特征，而不是成人的多形性浸润：来自动物模型的证据。AMJ生理学胃肠病肝生理学303：G93-G102,2012。2012年4月26日首次出版；doi：10.1152/ajpgi.00016.2012。-坏死性小肠结肠炎(NEC)是早产儿的一种炎症性肠坏死。在NEC的组织样本中，我们发现了大量的巨噬细胞和一些中性粒细胞，但没有太多的淋巴细胞。我们假设NEC的这些病理解剖特征代表了胃肠道在特定发育阶段对各种侮辱的一种常见的组织损伤反应。为了评估黏膜炎症反应的发育变化，我们使用三硝基苯磺酸(TNBS)诱导的炎症作为非特异性损伤，并比较了新生小鼠和成年小鼠的粘膜损伤。10日龄幼鼠和成年小鼠(每组25只)用TNBS灌胃和灌肠的方法诱发肠炎。用定量免疫荧光法对人NEC和小鼠TNBS-小肠结肠炎中的白细胞进行了计数。用定量聚合酶链式反应、免疫印迹和免疫组织化学方法检测趋化因子的表达。用肠组织条件培养液和骨髓来源的巨噬细胞在体外进行微量趋化试验，研究巨噬细胞的募集情况。与人类NEC相似，幼鼠的TNBS小肠结肠炎的特点是病变组织中有富含巨噬细胞的白细胞渗入。相反，成年小鼠的TNBS-小肠结肠炎与多形性白细胞浸润有关。巨噬细胞前体被趋化因子CXCL5招募到新生小鼠胃肠道，CXCL5是一种已知的髓系细胞趋化剂。我们还发现，在手术切除的人NEC组织样本中，CXCL5的表达增加，这表明在NEC中也存在类似的途径。我们的结论是，新生小鼠的肠粘膜损伤是以富含巨噬细胞的白细胞渗透为特征的，这与成年小鼠的多形性白细胞渗透形成了鲜明对比。在新生小鼠小肠结肠炎模型中，巨噬细胞被趋化因子CXCL5聚集到炎症的肠粘膜，表明CXCL5及其同源受体CXCR2是NEC潜在的治疗靶点，值得进一步研究。
MohanKumar K, Kaza N, Jagadeeswaran R, Garzon SA, Bansal A, Kurundkar AR, Namachivayam K, Remon JI, Bandepalli CR, Feng X, Weitkamp J-H, Maheshwari A. Gut mucosal injury in neonates is marked by macrophage infiltration in contrast to pleomorphic infiltrates in adult: evidence from an animal model. Am J Physiol Gastrointest Liver Physiol 303: G93-G102, 2012. First published April 26, 2012; doi:10.1152/ajpgi.00016.2012.-Necrotizing enterocolitis (NEC) is an inflammatory bowel necrosis of premature infants. In tissue samples of NEC, we identified numerous macrophages and a few neutrophils but not many lymphocytes. We hypothesized that these pathoanatomic characteristics of NEC represent a common tissue injury response of the gastrointestinal tract to a variety of insults at a specific stage of gut development. To evaluate developmental changes in mucosal inflammatory response, we used trinitrobenzene sulfonic acid (TNBS)-induced inflammation as a nonspecific insult and compared mucosal injury in newborn vs. adult mice. Enterocolitis was induced in 10-day-old pups and adult mice (n = 25 animals per group) by administering TNBS by gavage and enema. Leukocyte populations were enumerated in human NEC and in murine TNBS-enterocolitis using quantitative immunofluorescence. Chemokine expression was measured using quantitative polymerase chain reaction, immunoblots, and immunohistochemistry. Macrophage recruitment was investigated ex vivo using intestinal tissue-conditioned media and bone marrow-derived macrophages in a microchemotaxis assay. Similar to human NEC, TNBS enterocolitis in pups was marked by a macrophage-rich leukocyte infiltrate in affected tissue. In contrast, TNBS-enterocolitis in adult mice was associated with pleomorphic leukocyte infiltrates. Macrophage precursors were recruited to murine neonatal gastrointestinal tract by the chemokine CXCL5, a known chemoattractant for myeloid cells. We also demonstrated increased expression of CXCL5 in surgically resected tissue samples of human NEC, indicating that a similar pathway was active in NEC. We concluded that gut mucosal injury in the murine neonate is marked by a macrophage-rich leukocyte infiltrate, which contrasts with the pleomorphic leukocyte infiltrates in adult mice. In murine neonatal enterocolitis, macrophages were recruited to the inflamed gut mucosa by the chemokine CXCL5, indicating that CXCL5 and its cognate receptor CXCR2 merit further investigation as potential therapeutic targets in NEC.