Windbichler Michaela, Echtenacher Bernd, Takahashi Kazue, Ezekowitz R Alan B, Schwaeble Wilhelm J, Jenseniuis Jens C, Männel Daniela N
Institute of Immunology, University of Regensburg, Regensburg, Germany, and Department of Pediatrics, Laboratory of Developmental Immunology, Massachusetts General Hospital, Boston, USA.
Int Arch Allergy Immunol. 2006;141(1):11-23. doi: 10.1159/000094177. Epub 2006 Jun 23.
Systemic anaphylaxis is the most severe form of immediate hypersensitivity reaction. The activation of the complement system occurs during anaphylactic shock. The purpose of this study was to determine in a mouse model whether the lectin pathway of complement activation is involved in anaphylaxis.
To see whether the lectin pathway is involved in anaphylactic shock, serum mannan-binding lectin (MBL) levels were measured after passive anaphylaxis. Also MBL expression and binding to potential ligands were investigated. To determine whether complement or mast cell activation is essential for hypothermia in anaphylactic shock, mouse strains deficient in MBL-A and MBL-C, C1q, factors B and C2, C5, C5aR, or mast cells were tested.
After antigenic challenge a marked drop in body temperature as well as a rapid decrease in serum MBL levels were observed. The decrease of serum MBL levels in shock could not be attributed to MBL binding to immune complexes or tissues, but an interaction of MBL with mast cell-derived proteoglycans was seen. In contrast to mast cell-deficient mice, none of the complement-deficient mouse strains were protected from shock-associated hypothermia.
These results indicate that neither MBL nor activation of the complement cascade is crucial for the induction of anaphylaxis. In contrast mast cell activation is associated with the development of hypothermia and possibly the observed decrease in serum MBL levels.
全身性过敏反应是速发型超敏反应最严重的形式。补体系统的激活发生在过敏性休克期间。本研究的目的是在小鼠模型中确定补体激活的凝集素途径是否参与过敏反应。
为了观察凝集素途径是否参与过敏性休克,在被动过敏反应后测量血清甘露聚糖结合凝集素(MBL)水平。还研究了MBL的表达及其与潜在配体的结合。为了确定补体或肥大细胞激活对于过敏性休克中的体温过低是否至关重要,对缺乏MBL-A和MBL-C、C1q、因子B和C2、C5、C5aR或肥大细胞的小鼠品系进行了测试。
抗原攻击后,观察到体温显著下降以及血清MBL水平迅速降低。休克时血清MBL水平的降低不能归因于MBL与免疫复合物或组织的结合,但可见MBL与肥大细胞衍生的蛋白聚糖相互作用。与缺乏肥大细胞的小鼠不同,没有一种补体缺陷小鼠品系能免受休克相关的体温过低影响。
这些结果表明,MBL和补体级联的激活对于过敏反应的诱导都不是至关重要的。相反,肥大细胞激活与体温过低的发生以及可能观察到的血清MBL水平降低有关。