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

We recently demonstrated that intravenous (i.v.) injection of the iron-bind ing protein lactoferrin (Lf) followed by antilactoferrin (aLf) antibodies o r iron-saturated Lf alone increased albumin extravasation in vivo in severa l tissues including skin. Increased driving pressure for blood-tissue excha nge or direct effects of Lf on the endothelial barrier are possible mechani sms. We therefore, firstly. measured interstitial fluid pressure (P-if) in dermis of rats given 1 mg Lf i.v. followed 30 min later by aLf or saline an d circulatory arrest 1 or 5 min thereafter and compared with controls. Seco ndly, transmonolayer passage of Evans blue labelled albumin (EB-albumin) wa s evaluated in porcine pulmonary artery endothelial cells exposed to iron-f ree or iron-saturated Lf (both 100 mug mL(-1)) in the absence and presence of 0.5 mM hydrogen peroxide. P-if increased significantly at 11-30 min foll owing Lf to +2.1 +/- 0.3 and +1.7 +/- 0.2 mmHg at 11-20 and 21-30 min, resp ectively, compared with +0.1 +/- 0.2 mmHg before Lf (P < 0.05, n = 25). End othelial transmonolayer passage of EB-albumin during 3 h was not affected b y iron-free or iron-saturated Lf neither in the absence nor presence of hyd rogen 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 P-if (because Lf raised P-if significantly) or dir ect effects of Lf on the endothelial barrier.