Department of Anesthesia and Intensive Care, Haukeland University Hospital, Department of Biomedicine, University of Bergen, Bergen, Norway.
Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1864-70. doi: 10.1161/ATVBAHA.109.194308. Epub 2009 Sep 3.
Collagen-binding integrins may be involved in controlling interstitial fluid pressure (Pif), transcapillary fluid flux, and tissue fluid volume. Our aim was to explore whether the newly discovered collagen binding alpha11beta1 integrin has a mechanistic role in inflammatory edema formation.
In collagen matrices seeded with a mixture of mast cells and fibroblasts, fibroblasts lacking the alpha11 integrin subunit (alpha11(-/-)) contracted collagen gels less efficiently than control fibroblasts, suggesting that the alpha11beta1 integrin is able to mediate tensile force in connective tissues. In alpha11(-/-) mice, control Pif in skin did not differ from the pressure found in wild-type mice. Whereas a reduction in Pif was found in control mice after inducing inflammation, thereby contributing to fluid extravasation and edema formation, such a reduction was not seen in alpha11(-/-) mice. That this effect is mediated through the extracellular compartment is suggested by a similar plasma protein extravasation ratio in alpha11(-/-) and wild-type mice.
Our data suggest that alpha11beta1 integrins on dermal fibroblasts mediate collagen lattice remodeling and have a mechanistic role in controlling Pif in inflammation and thereby fluid extravasation and edema formation in vivo.
胶原蛋白结合整合素可能参与控制细胞间液压力(Pif)、跨毛细血管流体通量和组织液体积。我们的目的是探讨新发现的胶原蛋白结合α11β1 整合素在炎症性水肿形成中是否具有机械作用。
在含有肥大细胞和成纤维细胞混合物的胶原蛋白基质中,缺乏α11 整合素亚基(α11(-/-))的成纤维细胞比对照成纤维细胞收缩胶原蛋白凝胶的效率更低,这表明α11β1 整合素能够介导结缔组织中的张力。在α11(-/-)小鼠中,皮肤中的对照 Pif 与在野生型小鼠中发现的压力没有差异。虽然在诱导炎症后,对照小鼠中的 Pif 降低,从而导致液体渗出和水肿形成,但在α11(-/-)小鼠中未观察到这种降低。这种作用是通过细胞外隔室介导的,这表明α11(-/-)和野生型小鼠之间的血浆蛋白渗出比例相似。
我们的数据表明,真皮成纤维细胞上的α11β1 整合素介导胶原蛋白格子重塑,并在控制炎症中的 Pif 以及体内液体渗出和水肿形成中具有机械作用。