Choi E S, Pierce E M, Jakubzick C, Carpenter K J, Kunkel S L, Evanoff H, Martinez F J, Flaherty K R, Moore B B, Toews G B, Colby T V, Kazerooni E A, Gross B H, Travis W D, Hogaboam C M
Department of Pathology, University of Michigan Medical School, Room 5214, Medical Science I, 1301 Catherine Road, Ann Arbor, MI 48109-0602, USA.
J Clin Pathol. 2006 Jan;59(1):28-39. doi: 10.1136/jcp.2005.026872.
BACKGROUND/AIMS: Idiopathic interstitial pneumonias (IIPs) are a diverse grouping of chronic pulmonary diseases characterised by varying degrees of pulmonary fibrosis. The triggers of the fibroproliferative process in IIP remain enigmatic but recent attention has been directed towards chemokine involvement in this process.
The expression of two chemokine receptors, CCR7 and CXCR4, and their respective ligands, CCL19, CCL21, and CXCL12, were examined in surgical lung biopsies (SLBs) from patients with IIP. Transcript and protein expression of these receptors and their ligands was compared with that detected in histologically normal margin SLBs.
CCR7 and CXCR4 were detected by gene array and real time polymerase chain reaction analysis and CCR7, but not CXCR4, expression was significantly raised in usual interstitial pneumonia (UIP) relative to biopsies from patients diagnosed with non-specific interstitial pneumonia (NSIP) or respiratory bronchiolitis/interstitial lung disease (RBILD). CCR7 protein was expressed in interstitial areas of all upper and lower lobe UIP SLBs analysed. CCR7 expression was present in 50% of NSIP SLBs, and CCR7 was restricted to blood vessels and mononuclear cells in 75% of RBILD SLBs. Immune cell specific CXCR4 expression was seen in IIP and normal margin biopsies. CCR7 positive areas in UIP biopsies were concomitantly positive for CD45 (the leucocyte common antigen) but CCR7 positive areas in all IIP SLBs lacked the haemopoietic stem cell antigen CD34, collagen 1, and alpha smooth muscle actin.
This molecular and immunohistochemical analysis showed that IIPs are associated with abnormal CCR7 transcript and protein expression.
背景/目的:特发性间质性肺炎(IIP)是一组多样的慢性肺部疾病,其特征为不同程度的肺纤维化。IIP中纤维增殖过程的触发因素仍然不明,但最近人们的注意力已转向趋化因子在此过程中的作用。
检测了IIP患者手术肺活检(SLB)中两种趋化因子受体CCR7和CXCR4及其各自配体CCL19、CCL21和CXCL12的表达。将这些受体及其配体的转录本和蛋白表达与组织学正常边缘SLB中检测到的表达进行比较。
通过基因芯片和实时聚合酶链反应分析检测到CCR7和CXCR4,与诊断为非特异性间质性肺炎(NSIP)或呼吸性细支气管炎/间质性肺病(RBILD)患者的活检相比,寻常型间质性肺炎(UIP)中CCR7而非CXCR4的表达显著升高。分析的所有上、下叶UIP SLB的间质区域均表达CCR7蛋白。50%的NSIP SLB中有CCR7表达,75%的RBILD SLB中CCR7仅限于血管和单核细胞。在IIP和正常边缘活检中可见免疫细胞特异性CXCR4表达。UIP活检中CCR7阳性区域同时CD45(白细胞共同抗原)呈阳性,但所有IIP SLB中CCR7阳性区域缺乏造血干细胞抗原CD34、胶原蛋白1和α平滑肌肌动蛋白。
这种分子和免疫组织化学分析表明,IIP与CCR7转录本和蛋白表达异常有关。