Larsen Christen P, Regal Jean F
Department of Pharmacology and Toxicology Graduate Program, University of Minnesota, Duluth, 55812, USA.
Int Arch Allergy Immunol. 2002 Jan;127(1):63-72. doi: 10.1159/000048170.
In humans the incidence of asthma changes with age and gender. Immature guinea pigs have been used to model the allergic response to the occupational allergen trimellitic anhydride (TMA) where exposure to adults is paramount. We hypothesized that the TMA-induced allergic response in immature guinea pigs was similar to mature animals, regardless of gender.
Sexually immature and mature female and male guinea pigs were sensitized intradermally with TMA. Three weeks after sensitization they were challenged intratracheally with TMA conjugated to guinea pig serum albumin (TMA-GPSA) or GPSA as a control. Twenty-four hours later cell infiltration into the lung was determined. TMA-specific IgG(1) and IgG(2) were measured in plasma and the complement activation product C3a was measured in the bronchoalveolar lavage fluid.
In control animals, numbers of eosinophils and neutrophils varied with age and gender. The TMA-GPSA- induced cellular infiltration was similar in all age/gender groups. However, neutrophils in the lung tissue increased only in immature animals. IgG antibodies differed between groups but did not account for differences in cell infiltration. C3a correlated with the extent of cell infiltration in all groups except mature females.
TMA-induced neutrophilia differs with age. TMA-induced changes in eosinophils and macrophages did not vary with age or gender. The relationship between complement activation and inflammation in mature females differs from that in the other groups, suggesting mediators of the response may change with age and gender. Effects of age and gender need to be considered in animal models of the allergic response.
在人类中,哮喘的发病率随年龄和性别而变化。未成熟豚鼠已被用于模拟对职业过敏原偏苯三酸酐(TMA)的过敏反应,其中对成年动物的暴露至关重要。我们假设,无论性别如何,未成熟豚鼠中TMA诱导的过敏反应与成熟动物相似。
对性未成熟和成熟的雌性及雄性豚鼠进行TMA皮内致敏。致敏三周后,用与豚鼠血清白蛋白结合的TMA(TMA-GPSA)或作为对照的GPSA经气管内激发。24小时后测定肺内细胞浸润情况。检测血浆中TMA特异性IgG(1)和IgG(2),并测定支气管肺泡灌洗液中补体激活产物C3a。
在对照动物中,嗜酸性粒细胞和中性粒细胞的数量随年龄和性别而变化。TMA-GPSA诱导的细胞浸润在所有年龄/性别组中相似。然而,肺组织中的中性粒细胞仅在未成熟动物中增加。IgG抗体在各组之间存在差异,但不能解释细胞浸润的差异。除成熟雌性外,C3a与所有组中的细胞浸润程度相关。
TMA诱导的中性粒细胞增多随年龄而异。TMA诱导的嗜酸性粒细胞和巨噬细胞变化不随年龄或性别而变化。成熟雌性中补体激活与炎症之间的关系与其他组不同,提示反应的介质可能随年龄和性别而变化。在过敏反应的动物模型中需要考虑年龄和性别的影响。