Smith P D, Ohura K, Masur H, Lane H C, Fauci A S, Wahl S M
J Clin Invest. 1984 Dec;74(6):2121-8. doi: 10.1172/JCI111637.
The ineffective immune response in patients with the acquired immune deficiency syndrome (AIDS) contributes to severe and widespread infections and unrestricted growth by certain tumors. To determine whether monocyte dysfunction contributes to this immunosuppressed condition, we investigated monocyte chemotaxis in patients with AIDS. Using three different chemotactic stimuli, N-formylmethionylleucylphenylalanine, lymphocyte-derived chemotactic factor, and C5a des Arg, we studied the chemotactic responses of monocytes from seven homosexual men with AIDS, three homosexuals with lymphadenopathy and an abnormal immunological profile, seven healthy homosexual men, and 23 heterosexual control individuals. Monocytes from each of the AIDS patients with Kaposi's sarcoma and/or opportunistic infection exhibited a marked reduction in chemotaxis to all stimuli compared with the healthy control subjects. The reduced chemotactic responses were observed over a wide range of concentrations for each stimulus. Monocytes from AIDS patients who had clinically apparent opportunistic infection(s) exhibited a greater reduction in monocyte migration to all three stimuli than monocytes from the AIDS patient with only Kaposi's sarcoma. Monocytes from each of three homosexuals with lymphadenopathy and an abnormal immunological profile exhibited decreased chemotactic responses that were intermediate between those of the AIDS patients and the healthy heterosexual control subjects. In contrast to these findings, monocytes from each of seven healthy homosexuals exhibited normal chemotactic responses to the same stimuli. In addition, monocytes from AIDS patients exhibited reduced chemotaxis to soluble products of Giardia lamblia, one of several protozoan parasites prevalent in AIDS patients. Thus the immune abnormality in AIDS, previously thought to involve only the T-, B-, and natural killer lymphocytes, extends to the monocyte-macrophage. Defective monocyte migratory function may contribute to the depressed inflammatory response to certain organisms and to the apparent unrestricted growth of certain neoplasms in patients with AIDS.
获得性免疫缺陷综合征(艾滋病)患者的无效免疫反应会导致严重且广泛的感染以及某些肿瘤不受限制地生长。为了确定单核细胞功能障碍是否导致这种免疫抑制状态,我们研究了艾滋病患者的单核细胞趋化性。我们使用三种不同的趋化刺激物,即N - 甲酰甲硫氨酰亮氨酰苯丙氨酸、淋巴细胞衍生趋化因子和C5a去精氨酸,研究了7名患艾滋病的同性恋男性、3名有淋巴结病且免疫谱异常的同性恋者、7名健康同性恋男性以及23名异性恋对照个体的单核细胞趋化反应。与健康对照受试者相比,每例患有卡波西肉瘤和/或机会性感染的艾滋病患者的单核细胞对所有刺激物的趋化性均显著降低。在每种刺激物的广泛浓度范围内均观察到趋化反应降低。有临床明显机会性感染的艾滋病患者的单核细胞对所有三种刺激物的迁移减少程度大于仅患有卡波西肉瘤的艾滋病患者的单核细胞。3名有淋巴结病且免疫谱异常的同性恋者的单核细胞趋化反应降低,其程度介于艾滋病患者和健康异性恋对照受试者之间。与这些发现相反,7名健康同性恋者的单核细胞对相同刺激物表现出正常的趋化反应。此外,艾滋病患者的单核细胞对贾第鞭毛虫的可溶性产物趋化性降低,贾第鞭毛虫是艾滋病患者中普遍存在的几种原生动物寄生虫之一。因此,先前认为仅涉及T细胞、B细胞和自然杀伤淋巴细胞的艾滋病免疫异常扩展到了单核细胞 - 巨噬细胞。单核细胞迁移功能缺陷可能导致艾滋病患者对某些病原体的炎症反应减弱以及某些肿瘤明显不受限制地生长。