HUMAN EOSINOPHILS EXPRESS TRANSFORMING GROWTH FACTOR-ALPHA

HUMAN EOSINOPHILS EXPRESS TRANSFORMING GROWTH FACTOR-ALPHA
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DOI:
10.1084/jem.172.3.673
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发表时间:
1990-09-01
影响因子:
15.3
通讯作者:
TODD, R
TODD, R
中科院分区:
医学1区
文献类型:
--
作者:
WONG, DTW;WELLER, PF;TODD, R

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转化生长因子α。(转化生长因子--α。)是一种具有多种生物学效应的胸膜潜在细胞因子,包括影响正常细胞或肿瘤上皮细胞增殖的能力。嗜酸性粒细胞是粒细胞的一个亚群,通常进入周围组织,特别是胃肠道、呼吸道和泌尿生殖器上皮下的组织,它们居住在靠近上皮细胞的地方。在这项研究中,我们证明了绝大多数嗜酸性粒细胞渗入两个结肠腺癌和两个口腔鳞状细胞癌旁的间质组织,这是通过与人转化生长因子-α的35S-核探针进行原位杂交而标记的。(HTGF-α)。在这些病变中,没有其他可识别的白细胞含有可检测到的hTGF-α。MRNA.我们还检查了从一名特发性高嗜酸性粒细胞综合征患者中提纯的白细胞。80%的嗜酸性粒细胞,但没有患者的中性粒细胞或单核细胞,hTGF-α阳性。免疫组织化学染色显示,55%的嗜酸性粒细胞呈阳性反应。多肽。最后,将纯化的嗜酸性粒细胞相关转录物鉴定为hTGF-α。经聚合酶链式反应产物限制性内切酶分析和Southern印迹杂交证实。与高嗜酸性粒细胞综合征患者的嗜酸性粒细胞不同,7名正常献血者中只有2名外周血嗜酸性粒细胞可检测到转化生长因子-α。这些嗜酸性粒细胞均不含有免疫组织化学可检测到的转化生长因子-α。产品。综上所述,这些发现证实人类嗜酸性粒细胞可以表达转化生长因子-α,但提示转化生长因子-α的表达。嗜酸性粒细胞可能受到微环境的调节。转化生长因子-α的演示。通过组织浸润性嗜酸性粒细胞的产生和高嗜酸性粒细胞综合征中的嗜酸性粒细胞确定了一种新的机制,即嗜酸性粒细胞可能有助于生理、免疫和病理反应。
Transforming growth factor .alpha. (TGF-.alpha.) is a pleuripotential cytokine with diverse biological effects, including the ability to influence the proliferation of normal cells or neoplastic epithelial cells. Eosinophils are a subset of granulocytes that normally enter the peripheral tissues, particularly those beneath gastrointestinal, respiratory, and urogenital epithelium, where they reside in close proximity to the epithelial elements. In this study, we demonstrate that the great majority of eosinophils infiltrating the interstitial tissues adjacent to two colonic adenocarcinomas and two oral squamous cell carcinomas labeled specifically by in situ hybridization with a 35S-riboprobe for human TGF-.alpha. (hTGF-.alpha.). No other identifiable leukocytes in these lesions contained detectable hTGF-.alpha. mRNA. We also examined leukocytes purified from a patient with the idiopathic hypereosinophilic syndrome. 80% of these eosinophils, but none of the patients'' neutrophils or mononuclear cells, were positive for hTGF-.alpha. mRNA by in situ hybridization, and 55% of these eosinophils were positive by immunohistochemistry with a monoclonal antibody directed against the COOH terminus of the mature hTGF-.alpha. peptide. Finally, the idneitification of the purified eosinophil-associated transcript as hTGF-.alpha. was confirmed by polymerase chain reaction product restriction enzyme analysis followed by Southern blot hybridization. In contrast to eosinophils from the patient with hypereosinophilic syndrome, the peripheral blood eosinophils from only two of seven normal donors had detectable TGF-.alpha. mRNA and none of these eosinophils contained immunohistochemically detectable TGF-.alpha. product. Taken together, these findings establish that human eosinophils can express TGF-.alpha., but suggest that the expression of TGF-.alpha. by eosinophils may be under microenvironmental regulation. Demonstration of TGF-.alpha. production by tissue-infiltrating eosinophils and the eosinophils in the hypereosinophilic syndrome identifies a novel mechanism by which eosinophils might contribute to physiological, immunological, and pathological responses.