Stanton Lee-Anne, Fenhalls Gael, Lucas Andrew, Gough Peter, Greaves David R, Mahoney James A, Helden Paul van, Gordon Siamon
Department of Medical Biochemistry, Tygerberg Medical School University of Stellenbosch, Tygerberg, South Africa.
Int J Exp Pathol. 2003 Dec;84(6):289-304. doi: 10.1111/j.0959-9673.2003.00365.x.
Classic studies of tuberculosis (TB) revealed morphologic evidence of considerable heterogeneity of macrophages (MØs), but the functional significance of this heterogeneity remains unknown. We have used newly available specific antibodies for selected membrane and secretory molecules to examine the phenotype of MØs in situ in a range of South African patients with TB, compared with sarcoidosis. Patients were human immunodeficiency virus-negative adults and children, and the examined biopsy specimens included lung and lymph nodes. Mature pulmonary MØs (alveolar, interstitial, epithelioid and multinucleated giant cells) selectively expressed scavenger receptor type A and a novel carboxypeptidase-like antigen called carboxypeptidase-related vitellogenin-like MØ molecule (CPVL). CPVL did not display enhanced expression in sarcoidosis, vs. TB patients, as observed with angiotensin-converting enzyme (ACE), a related molecule. Immunocytochemical studies with surfactant proteins (SP)-A and -D showed that type II alveolar cells expressed these collectins, as did MØs, possibly after binding of secreted proteins. Studies with an antibody specific for the C-terminus of fractalkine, a tethered CX3C chemokine, confirmed synthesis of this molecule by bronchiolar epithelial cells and occasional endothelial cells. These studies provide new marker antigens and extend previous studies on MØ differentiation, activation and local interactions in chronic human granulomatous inflammation in the lung.
结核病(TB)的经典研究揭示了巨噬细胞(MØs)存在显著异质性的形态学证据,但这种异质性的功能意义仍不明确。我们使用了针对选定膜分子和分泌分子的新型特异性抗体,来检测一系列南非结核病患者以及结节病患者原位MØs的表型。患者为人类免疫缺陷病毒阴性的成人和儿童,所检测的活检标本包括肺和淋巴结。成熟的肺MØs(肺泡、间质、上皮样和多核巨细胞)选择性表达A类清道夫受体和一种名为羧肽酶相关卵黄生成素样MØ分子(CPVL)的新型羧肽酶样抗原。与相关分子血管紧张素转换酶(ACE)不同,在结节病患者与结核病患者中,CPVL并未表现出表达增强。用表面活性蛋白(SP)-A和-D进行的免疫细胞化学研究表明,II型肺泡细胞表达这些凝集素,MØs也表达,可能是在分泌蛋白结合之后。用一种针对CX3C趋化因子fractalkine C末端的特异性抗体进行的研究证实,细支气管上皮细胞和偶尔的内皮细胞可合成该分子。这些研究提供了新的标记抗原,并扩展了之前关于肺慢性人类肉芽肿性炎症中MØ分化、激活和局部相互作用的研究。