Kaplan Barbara L F, Lawver Jody E, Karmaus Peer W F, Ngaotepprutaram Thitirat, Birmingham Neil P, Harkema Jack R, Kaminski Norbert E
Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824, USA.
Toxicol Pathol. 2010 Apr;38(3):382-92. doi: 10.1177/0192623310362706. Epub 2010 Feb 26.
The mechanisms by which cannabinoid receptors CB(1) and CB(2) modulate immune function are not fully elucidated. Critical tools for the determination of the role of both receptors in the immune system are CB(1)/CB(2) double null mice (CB(1)/CB(2) null), and previous studies have shown that CB(1)/CB(2) null mice exhibit exaggerated responses to various immunological stimuli. The objective of these studies was to determine the magnitude to which CB(1)/CB(2) null mice responded to the respiratory allergen ovalbumin (OVA) as compared with wild-type C57BL/6 mice. The authors determined that in the absence of adjuvant, both wild-type and CB(1)/CB(2) null mice mounted a marked response to intranasally instilled OVA as assessed by inflammatory cell infiltrate in the bronchoalveolar lavage fluid (BALF), eosinophilia, induction of mucous cell metaplasia, and IgE production. Many of the endpoints measured in response to OVA were similar in wild-type versus CB(1)/CB(2) null mice, with exceptions being modest reductions in OVA-induced IgE and attenuation of BALF neutrophilia in CB(1)/CB(2) null mice as compared with wild-type mice. These results suggest that T-cell responses are not universally exaggerated in CB(1)/CB(2) null mice.
大麻素受体CB(1)和CB(2)调节免疫功能的机制尚未完全阐明。确定这两种受体在免疫系统中作用的关键工具是CB(1)/CB(2)双敲除小鼠（CB(1)/CB(2)敲除小鼠），先前的研究表明，CB(1)/CB(2)敲除小鼠对各种免疫刺激表现出过度反应。这些研究的目的是确定与野生型C57BL/6小鼠相比，CB(1)/CB(2)敲除小鼠对呼吸道过敏原卵清蛋白（OVA）的反应程度。作者确定，在没有佐剂的情况下，通过支气管肺泡灌洗液（BALF）中的炎性细胞浸润、嗜酸性粒细胞增多、黏液细胞化生的诱导和IgE产生评估，野生型和CB(1)/CB(2)敲除小鼠对鼻内滴注的OVA均产生明显反应。野生型与CB(1)/CB(2)敲除小鼠中许多针对OVA测量的终点相似，但与野生型小鼠相比，CB(1)/CB(2)敲除小鼠中OVA诱导的IgE有适度降低，BALF中性粒细胞增多有所减轻。这些结果表明，CB(1)/CB(2)敲除小鼠中的T细胞反应并非普遍过度。
