NEM and filipin increase albumin transport in lung microvessels

This study was undertaken to evaluate the role of transcytosis as a bulk transfer mechanism for the passage of albumin from blood to tissue. Isolated rat lungs were continuously weighed and perfused with an albumin-serum buffer solution under strictly controlled hemodynamic conditions, which allowed measurements of microvascular pressure and of the capillary filtration coefficient (L(p)S). With the use of a tissue uptake technique, it was possible to determine lung albumin clearance under isogravimetric conditions (Cl(iso)), or at elevated filtration rates, to obtain an "apparent albumin reflection coefficient" (sigma(alb)). Experiments were performed during control and after reducing lung temperature from 35 degrees to 22 degrees C and after infusions of the transcytosis inhibitors N-ethylmaleimide (NEM) or filipin. Cooling moderately increased vascular resistance and reduced L(p)S and Cl(iso) largely in proportion to the induced increases in viscosity. At 35 degrees C, NEM (0.13 mM) caused a marked increase in L(p)5 and in Cl(150) and also caused a reduction in sigma(alb.) Furthermore, Cl(iso) increased for the highest dose of filipin tested (1.8 microg/ml). The demonstrated relative cooling insensitivity of the transfer of albumin across the endothelium in rat lungs does not support the contention of transcytosis of proteins across the endothelium. Furthermore, neither NEM nor filipin inhibited lung microvascular albumin transport, but actually increased lung endothelial permeability.