Johnson Victor J, Walker Nigel J, Luster Michael I, Burleson Gary R, Cora Michelle, Baker Gregory L, Sparrow Barney, Germolec Dori R
Burleson Research Technologies, Inc., Morrisville, NC, United States.
Division of Translational Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, United States.
Front Toxicol. 2025 May 26;7:1539810. doi: 10.3389/ftox.2025.1539810. eCollection 2025.
Several lines of evidence suggest the possibility that inhalation exposure to multi-walled carbon nanotubes (MWCNT) at occupationally relevant doses can lead to systemic immunotoxicity. To test this hypothesis, we undertook in-depth examination of immune function in mice and rats exposed by inhalation to relatively low levels of 1020 Long Multiwalled Carbon Nanotubes (L-MWNT-1020).
Studies were conducted to determine the systemic and pulmonary immunotoxic effects in mice and rats exposed to L-MWNT-1020 following whole-body inhalation for 6 h/day for 5 days/week for 30 (mice and rats) and 90 (mice) days at dose levels of 0, 0.06, 0.2, and 0.6 mg/m. Additional groups were administered cyclophosphamide (CPS) as a positive control for each cohort. Following exposure, pulmonary macrophage phagocytosis, immunophenotypic analysis of immune cells populations in the spleen, and systemic immune function, including tests for humoral (T-dependent antibody response, TDAR), cell-mediated (cytotoxic T-lymphocyte [CTL] activity), and innate (Natural Killer [NK] cell activity) immunity were conducted.
While exposure increased pulmonary macrophage activity, no major changes were observed in any of the systemic immune parameters measured in mice exposed for 30 or 90 days. In rats, there was a slight decrease in humoral immunity coinciding with an increase in the number of splenic T cell and NK cell populations.
Although pulmonary macrophage activity increased in mice following exposure to L-MWNT-1020, systemic immune function for the most part remained unaffected. In contrast, rats demonstrated a slight decrease in humoral immune function as well as an increase in spleen cell numbers, T cell, and NK cell populations suggesting species-specific effects on systemic immunity, however, these effects were small and their biological significance with respect to altering disease susceptibility is unclear.
多项证据表明，职业相关剂量下吸入多壁碳纳米管（MWCNT）可能导致全身免疫毒性。为验证这一假设，我们对吸入相对低水平的1020长多壁碳纳米管（L-MWNT-1020）的小鼠和大鼠的免疫功能进行了深入研究。
进行研究以确定小鼠和大鼠在全身吸入L-MWNT-1020后，在剂量水平为0、0.06、0.2和0.6毫克/立方米的情况下，每天6小时、每周5天、持续30天（小鼠和大鼠）和90天（小鼠）后的全身和肺部免疫毒性作用。每个队列另外设置给予环磷酰胺（CPS）的组作为阳性对照。暴露后，进行肺部巨噬细胞吞噬作用、脾脏免疫细胞群体的免疫表型分析以及全身免疫功能检测，包括体液免疫（T细胞依赖性抗体反应，TDAR）、细胞介导免疫（细胞毒性T淋巴细胞[CTL]活性）和固有免疫（自然杀伤[NK]细胞活性）检测。
虽然暴露增加了肺部巨噬细胞活性，但在暴露30天或90天的小鼠中，所测量的任何全身免疫参数均未观察到重大变化。在大鼠中，体液免疫略有下降，同时脾脏T细胞和NK细胞群体数量增加。
虽然小鼠暴露于L-MWNT-1020后肺部巨噬细胞活性增加，但全身免疫功能在很大程度上仍未受影响。相比之下，大鼠表现出体液免疫功能略有下降以及脾细胞数量、T细胞和NK细胞群体增加，表明对全身免疫有物种特异性影响，然而，这些影响较小，其对改变疾病易感性的生物学意义尚不清楚。
