Keshav S, Chung P, Milon G, Gordon S
Sir William Dunn School of Pathology, University of Oxford, United Kingdom.
J Exp Med. 1991 Nov 1;174(5):1049-58. doi: 10.1084/jem.174.5.1049.
This study demonstrates the induction of lysozyme mRNA expression in situ in tissue macrophages (M phi) of mice following in vivo stimulation. The resting resident tissue M phi of most tissues do not contain enough lysozyme mRNA to be detected by in situ hybridization using 35S-labeled RNA probes. Following Bacille Calmette Guerin or Plasmodium yoelli infection, however, M phi recruited to liver and spleen hybridize strongly to the lysozyme probe. Within 24 h of infection, cells found in the marginal zone of the spleen begin to produce lysozyme mRNA. This response is also evoked by a noninfectious agent (intravenously injected sheep erythrocytes), and is possibly the result of an early phagocytic interaction. Later in the infection, other cells in the red and white pulp of the spleen, and cells in granulomas in the liver, become lysozyme-positive. Kupffer cells are rarely lysozyme-positive. Lysozyme mRNA levels in liver granulomas remain relatively constant during the infection, and lysozyme is produced by most granuloma cells. This contrasts with tumor necrosis factor alpha (TNF alpha) mRNA, which is produced by fewer cells in the granuloma, and which can be massively induced by lipopolysaccharide administration. The production of lysozyme, previously considered a constitutive function of M phi, is therefore an indicator of M phi activation in vivo, where immunologically specific and nonspecific stimuli both stimulate lysozyme production at high levels in subpopulations of cells occupying discrete anatomical locations.
本研究证明,在体内刺激后,小鼠组织巨噬细胞(M phi)中可原位诱导溶菌酶mRNA表达。大多数组织中静止的驻留组织M phi所含的溶菌酶mRNA不足以通过使用35S标记的RNA探针进行原位杂交来检测。然而,在卡介苗或约氏疟原虫感染后,募集到肝脏和脾脏的M phi与溶菌酶探针强烈杂交。感染后24小时内,脾脏边缘区发现的细胞开始产生溶菌酶mRNA。这种反应也可由非感染性因子(静脉注射绵羊红细胞)诱发,可能是早期吞噬相互作用的结果。在感染后期,脾脏红髓和白髓中的其他细胞以及肝脏肉芽肿中的细胞变为溶菌酶阳性。库普弗细胞很少呈溶菌酶阳性。在感染期间,肝脏肉芽肿中的溶菌酶mRNA水平保持相对恒定,并且大多数肉芽肿细胞产生溶菌酶。这与肿瘤坏死因子α(TNFα)mRNA形成对比,TNFαmRNA由肉芽肿中较少的细胞产生,并且可通过给予脂多糖大量诱导。因此,溶菌酶的产生以前被认为是M phi的组成性功能,是体内M phi激活的一个指标,在体内,免疫特异性和非特异性刺激均能在占据离散解剖位置的细胞亚群中高水平刺激溶菌酶的产生。