Post-BMT lung injury occurs independently of the expression of CCL2 or its receptor, CCR2, on host cells.
Post-BMT lung injury occurs independently of the expression of CCL2 or its receptor, CCR2, on host cells.
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BMT 后肺损伤的发生与宿主细胞上 CCL2 或其受体 CCR2 的表达无关。
DOI：
10.1152/ajplung.00154.2003
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
Blazar,BruceR
中科院分区：
文献类型：
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作者：
Panoskaltsis-Mortari,Angela;Hermanson,JohnR;Taras,Elizabeth;Wangensteen,ODouglas;Charo,IsraelF;Rollins,BarrettJ;Blazar,BruceR
特发性肺炎综合征（IPS）是人类骨髓移植（BMT）后死亡的重要原因。在我们的小鼠模型中，致死性预BMT调节和同种异体T细胞导致宿主抗原呈递细胞（APC）和供体T细胞募集到BMT后的肺中，伴随着严重肺功能障碍的发展。在宿主单核细胞流入之前，在支气管肺泡灌洗液（BALF）中发现了CCL 2诱导。CCL 2的主要受体是存在于单核细胞上的CCR 2;这种相互作用可以在炎症中的单核细胞募集中发挥关键作用。为了确定阻断CCL 2/CCR 2通路是否会阻碍宿主单核细胞流入，将同种异体骨髓和脾细胞移植到致死条件野生型（WT）、CCL 2-/-或CCR 2-/-小鼠。WT和-/-受体在BMT后表现出等同的肺功能障碍。WT和-/-受体之间BMT后肺中宿主巨噬细胞以及供体CD 4+和CD 8 +T细胞的频率没有差异。然而，宿主CD 11b+主要组织相容性复合物II类+细胞流入的T细胞依赖性在CCR 2-/-受体中丢失。在CCR 2-/-小鼠中，这种流入伴随着CCL 20水平的升高。与WT小鼠相比，-/-小鼠的BMT后BALF和血清中细胞因子或趋化因子未显示任何降低。CCL 2-/-小鼠BMT后BALF和血清中CCL 2缺乏，证实了我们的假设，即CCL 2主要来源于宿主。因此，IPS可以独立于CCL 2或CCR 2的宿主表达而发生，并且在BMT后早期期间存在用于调节APC募集到肺中的补偿机制。
Idiopathic pneumonia syndrome (IPS) is a significant cause of mortality post-bone marrow transplant (BMT) in humans. In our murine model, lethal pre-BMT conditioning and allogeneic T cells result in the recruitment of host antigen-presenting cells (APC) and donor T cells into the lung post-BMT concomitant with development of severe lung dysfunction. CCL2 induction is found in bronchoalveolar lavage fluid (BALF) before host monocyte influx. The major receptor for CCL2 is CCR2 present on monocytes; this interaction can play a crucial role in monocyte recruitment in inflammation. To determine whether blockade of the CCL2/CCR2 pathway could hinder host monocyte influx, lethally conditioned wild-type (WT), CCL2-/-, or CCR2-/-mice were transplanted with allogeneic marrow and spleen cells. WT and-/-recipients exhibited equivalent lung dysfunction post-BMT. The frequencies of host macrophages as well as donor CD4+and CD8+T cells in lungs post-BMT did not differ between WT and-/-recipients. However, the T cell dependency of the host CD11b+major histocompatibility complex class II+cell influx was lost in CCR2-/-recipients. In CCR2-/-mice, this influx was accompanied by elevated levels of CCL20. Post-BMT BALF and sera of-/-mice did not reveal any decrease in cytokines or chemokines compared with WT mice. CCL2-/-mice had a deficiency of CCL2 in their BALF and sera post-BMT, confirming our hypothesis that CCL2 is predominantly host derived. Therefore, IPS can occur independently of host expression of CCL2 or CCR2, and compensatory mechanisms exist for regulating APC recruitment into the lung during the early post-BMT period.