Kim Y K, Uno M, Hamilos D L, Beck L, Bochner B, Schleimer R, Denburg J A
Department of Otolaryngology, Inje University, Seoul, Korea.
Am J Respir Cell Mol Biol. 1999 Mar;20(3):388-97. doi: 10.1165/ajrcmb.20.3.3060.
Airway inflammation in patients with nasal polyps is characterized by the increased presence of eosinophils, the numbers of which are reduced after treatment with topical corticosteroids. Because eosinophilic responses in the airways are in part due to eosinophil progenitor differentiation, we hypothesized that CD34, a cell surface, sialomucinlike glycoprotein that specifically marks hemopoietic progenitors and endothelium, would be expressed in nasal polyp tissue. We sought to identify CD34(+) leukocytes or endothelial cells in nasal polyps. We also investigated the effect of the topical corticosteroid budesonide on the numbers of CD34(+) cells and vessels in nasal polyps. To accomplish this, we performed immunostaining for CD34 protein in tissue sections of nasal polyps from topical steroid-treated and -untreated groups of patients, as well as from one patient before and after systemic corticosteroid therapy. We also examined myeloid colony formation by isolated polyp mononuclear cells, and performed flow cytometry to detect the presence of CD34(+)/CD45(+) cells within these isolated populations. We also examined the in vitro effects of steroids on human umbilical vein endothelial cell (HUVEC) expression of CD34. We detected CD34-immunoreactive mononuclear cells and blood vessels in the lamina propria of all nasal polyps. CD34(+) mononuclear cells resembled immature hemopoietic cells morphologically. Mononuclear cell fractions from polyps contained myeloid colony-forming cells and cells bearing CD45, a pan-leukocyte marker, as well as CD34, and gated as true hemopoietic blast cells. The numbers of CD34(+) cells and CD34(+) vessels in steroid-treated nasal polyps were significantly higher than in steroid-untreated nasal polyps (15.67 +/- 2.08 cells/10 hpf, versus 5.33 +/- 1.36 cells/10 hpf, P = 0.002; 101.25 +/- 6.24 vessels/0.5 mm2 of lamina propria, versus 57.22 +/- 8.00 vessels/0.5 mm2 of lamina propria, P = 0.0008, respectively). A similar upregulation of CD34 immunostaining, especially for mononuclear cells, was observed in one patient after systemic corticosteroid therapy. Steroid treatment in vitro of HUVECs did not result in enhanced CD34 expression. Both CD34(+)/CD45(+) mononuclear cells and CD34(+) endothelial cells are present within nasal polyps, with higher numbers in patients who have received topical corticosteroid treatment. Because enhancement of CD34 expression was not seen in cultured umbilical vein endothelial cells treated in vitro with corticosteroid, the findings of the study suggest that in nasal polyp tissue, steroids enhance numbers of CD34(+) progenitors and endothelial cells via indirect mechanisms.
鼻息肉患者的气道炎症表现为嗜酸性粒细胞增多,局部使用糖皮质激素治疗后嗜酸性粒细胞数量减少。由于气道中的嗜酸性粒细胞反应部分归因于嗜酸性粒细胞祖细胞的分化,我们推测CD34(一种特异性标记造血祖细胞和内皮细胞的细胞表面唾液酸黏蛋白样糖蛋白)会在鼻息肉组织中表达。我们试图鉴定鼻息肉中的CD34(+)白细胞或内皮细胞。我们还研究了局部糖皮质激素布地奈德对鼻息肉中CD34(+)细胞和血管数量的影响。为此,我们对局部使用类固醇治疗组和未治疗组患者的鼻息肉组织切片以及一名接受全身糖皮质激素治疗前后的患者的鼻息肉组织切片进行了CD34蛋白免疫染色。我们还检测了分离的息肉单核细胞的髓系集落形成,并进行了流式细胞术以检测这些分离群体中CD34(+)/CD45(+)细胞的存在。我们还研究了类固醇对人脐静脉内皮细胞(HUVEC)CD34表达的体外影响。我们在所有鼻息肉的固有层中检测到了CD34免疫反应性单核细胞和血管。CD34(+)单核细胞在形态上类似于未成熟的造血细胞。息肉的单核细胞部分含有髓系集落形成细胞以及带有全白细胞标记CD45和CD34的细胞,并被分类为真正的造血母细胞。接受类固醇治疗的鼻息肉中CD34(+)细胞和CD34(+)血管的数量显著高于未接受类固醇治疗的鼻息肉(分别为15.67±2.08个细胞/10高倍视野,而5.33±1.36个细胞/10高倍视野,P = 0.002;固有层每0.5平方毫米101.25±6.24条血管,而每0.5平方毫米57.22±8.00条血管,P = 0.0008)。在一名接受全身糖皮质激素治疗的患者中,观察到了类似的CD34免疫染色上调,尤其是单核细胞。体外对HUVEC进行类固醇治疗并未导致CD34表达增强。鼻息肉中同时存在CD34(+)/CD45(+)单核细胞和CD34(+)内皮细胞,在接受局部糖皮质激素治疗的患者中数量更多。由于体外使用糖皮质激素处理的培养脐静脉内皮细胞中未观察到CD34表达增强,该研究结果表明,在鼻息肉组织中,类固醇通过间接机制增加了CD34(+)祖细胞和内皮细胞的数量。