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Effects of lactoferrin on rat dermal interstitial fluid pressure (Pif) and in vitro endothelial barrier function

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We recently demonstrated that intravenous (i.v.) injection of the iron-binding protein lactoferrin (Lf) followed by antilactoferrin (aLf) antibodies or iron-saturated Lf alone increased albumin extravasation in vivo in several tissues including skin. Increased driving pressure for blood-tissue exchange or direct effects of Lf on the endothelial barrier are possible mechanisms. We therefore, firstly, measured interstitial fluid pressure (Pif) in dermis of rats given 1 mg Lf i.v. followed 30 min later by aLf or saline and circulatory arrest 1 or 5 min thereafter and compared with controls. Secondly, transmonolayer passage of Evans blue labelled albumin (EB-albumin) was evaluated in porcine pulmonary artery endothelial cells exposed to iron-free or iron-saturated Lf (both 100 μg mL–1) in the absence and presence of 0.5 mMhydrogen peroxide. Pif increased significantly at 11–30 min following Lf to +2.1 ± 0.3 and +1.7 ± 0.2 mmHg at 11–20 and 21–30 min, respectively, compared with +0.1 ± 0.2 mmHg before Lf (P < 0.05, n=25). Endothelial transmonolayer passage of EB-albumin during 3 h was not affected by iron-free or iron-saturated Lf neither in the absence nor presence of hydrogen peroxide that increased passage 3.5 times compared with controls. In conclusion, Lf-induced increase in albumin extravasation in rat skin is not explained by changes in Pif (because Lf raised Pif significantly) or direct effects of Lf on the endothelial barrier.

Keywords: albumin permeability; cationic protein; endothelial monolayers; interstitial fluid pressure; lactoferrin; skin

Document Type: Research Article


Affiliations: 1: Department of Physiology, University of Bergen, Bergen, Norway 2: Department of Internal Medicine, University of Bergen, Bergen, Norway 3: Department of Pathology, University of Linkøping, Linkøping, Sweden

Publication date: April 1, 2001


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