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A Siflinger-Birnboim

Publications and source records attributed to A Siflinger-Birnboim.

17 recordsLinked to original sources
PubMed1996

Involvement of Ca2+ in the H2O2-induced increase in endothelial permeability.

We studied the role of Ca2+ in mediating the hydrogen peroxide (H2O2)-induced increase in endothelial permeability to 125I-labeled albumin using bovine pulmonary microvessel endothelial cells (BMVEC). Changes in cytosolic-free Ca2+ ([Ca2+]i) were monitored in BMVEC monolayers loaded with the Ca(2+)-sensitive membrane permeant fluorescent dye fura 2-AM. H2O2 (100 microM) produced a rise in [Ca2+]i within 10 s that was reduced by the addition of EGTA to the medium. Uptake of 45Ca2+ from the extracellular medium increased in the presence of H2O2 (100 microM) compared with control monolayers, suggesting that the H2O2-induced rise in [Ca2+]i is partly the result of extracellular Ca2+ influx. The effects of [Ca2+]i on endothelial permeability were addressed by pretreatment of BMVEC monolayers with BAPTA-AM (3-5 microM), a membrane permeant Ca2+ chelator, before the H2O2 exposure. BAPTA-AM produced an approximately 50% decrease in the H2O2-induced increase in endothelial permeability compared with endothelial cell monolayers exposed to H2O2 alone. The increase in endothelial permeability was independent of Ca2+ influx, since LaCl3 (0-100 microM), which displaces Ca2+ from binding sites on the cell surface, did not modify the permeability response. These results indicate that the rise in [Ca2+]i produced by H2O2 is a critical determinant of the increase in endothelial permeability.

Animals↗
PubMed1996

Regulation of endothelial permeability by second messengers.

The mechanisms by which mediators such as oxidants released by neutrophil (PMN) activation increase endothelial permeability are poorly understood. The focus of this article is to identify some of these mechanisms. Studies using endothelial cell monolayers in culture have shown that PMN activation increases endothelial permeability both in the presence and absence of PMN-endothelial monolayer contact. Hydrogen peroxide (H2O2), an oxidant released by PMN activation, plays an important role in PMN-induced increases in endothelial permeability. The results of these studies suggest that, as with other mediators of inflammation (e.g., histamine, thrombin) the mechanism of H2O2-induced increase in endothelial permeability involves activation of endothelial protein kinase C (PKC) and increase in endothelial cytosolic Ca2+.

Animals↗
PubMed1994

Segmental differentiation of permeability, protein glycosylation, and morphology of cultured bovine lung vascular endothelium.

The barrier function, surface biochemistry, and morphology of confluent monolayers of endothelial cells isolated from different segments of the bovine lung vasculature [microvessels (BLMVEC), vein (BPVEC) and artery (BPAEC)] were grown in culture and compared. A number of common cell surface proteins were identified along with two proteins of 46 and 48 kDa found exclusively on BPVEC. Lectin affinity chromatography revealed multiple glycosylation differences. The lectins, Arachis hypogaea (AHA) and Lycopersicum esculentum (LEA) agglutinins, interacted with several glycoproteins of BLMVEC but not of BPAEC. Bandeiraea simplicifolia (BS-1) and Caragana arborescens (CAA) agglutinins recognized several glycoproteins of BPVEC and BPAEC but not BLMVEC. Permeabilities were much lower for BLMVEC than BPAEC or BPVEC monolayers, with a range of about 16-fold less for sucrose to 2-fold less for albumin. Electron microscopy revealed that BLMVEC have a greater surface density of plasmalemmal vesicles (approximately 4-fold) and more extensively developed intercellular junctions with more focal membrane adhesion sites per junction (approximately 9-fold) than the other cells. We conclude that: i) BLMVEC monolayers form a much more restrictive barrier to molecular transport as a result of the tighter junctional formation; and ii) endothelial surface glycoproteins may be differentially glycosylated depending on their segmental location within the vasculature.

Animals↗
PubMed1993

Neutrophil adhesion to endothelial cells impairs the effects of catalase and glutathione in preventing endothelial injury.

We studied the effects of the CuZn superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) on endothelial permeability to 125I-albumin after activation of neutrophils (PMN) with phorbol 12-myristate-13-acetate (PMA; 10(-8) M). PMN were either in direct contact with the endothelial cell monolayer grown on a porous gelatin-coated microporous 10-microns-thick polycarbonate filter (upright system) or separated from the endothelium by a similar filter (inverted system). Transendothelial 125I-albumin clearance rates were measured as an index of endothelial permeability. In the absence of antioxidants, activation of PMN increased transendothelial 125I-albumin clearance rates in both systems from 0.041 +/- 0.006 microliters/min (baseline) to 0.262 +/- 0.18 microliters/min (upright system) and from 0.063 +/- 0.02 microliters/min to 0.244 +/- 0.06 microliters/min (inverted system). PMA induced 80-90% of PMN to adhere to either gelatin-coated filters or to endothelial cells, from the basal PMN adhesion value of 5.3 +/- 2.2% and 4.3 +/- 1.1%, respectively. SOD, which dismutases superoxide anion to hydrogen peroxide (H2O2), did not alter the transendothelial 125I-albumin clearance rates in either system at any concentration from 10-300 U/ml. CAT (100-1,000 U/ml) and GSH (0.5-10 mM), which remove the H2O2 generated during PMN activation, did not alter the increase in transendothelial 125I-clearance rates after PMN activation in the upright system, but both agents prevented the increase in transendothelial 125I-clearance rates in the inverted system. We conclude that PMN activation with PMA causes endothelial injury irrespective of PMN contact to the endothelial monolayer. Moreover, H2O2, a release product of PMN activation, is a critical mediator of PMN-dependent endothelial injury. Finally, the results indicate that CAT and GSH prevent endothelial injury only in the absence of direct PMN contact with endothelial cells, suggesting that antioxidants such as GSH and CAT are excluded from sites of PMN-endothelial contact and thus are ineffective antioxidants.

Animals↗
PubMed1993

Thrombin receptor peptide inhibits thrombin-induced increase in endothelial permeability by receptor desensitization.

Thrombin, a potent activator of cellular responses, proteolytically cleaves, and thereby activates its receptor. In the present study, we compared the effects of the thrombin receptor 14-amino acid peptide (TRP-14; SFLLRNPNDKYEPF), which comprises the NH2 terminus after cleavage of the thrombin receptor, and of the native alpha-thrombin on endothelial monolayer permeability. Addition of TRP-14 (1-200 microM) to bovine pulmonary artery endothelial cells increased [Ca2+]i in a dose-dependent manner. The peak increase in [Ca2+]i in response to 100 microM TRP-14 or 0.1 microM alpha-thrombin was similar (i.e., 931 +/- 74 nM and 1032 +/- 80 nM, respectively), which was followed by a slow decrease with t1/2 values of 0.73 and 0.61 min, respectively. Extracellular Ca2+ chelation with 5 mM EGTA abolished the sustained increases in [Ca2+]i induced by either TRP-14 or alpha-thrombin. alpha-thrombin (0.1 microM) increased transendothelial [125I]albumin permeability, whereas TRP-14 (1-100 microM) had no effect. Coincubation of 100 microM TRP-14 with 1 microM DIP-alpha-thrombin also did not increase permeability over control values. Stimulation of BPAEC with 0.1 microM alpha-thrombin induced translocation of protein kinase C (PKC) from the cytosol to the plasma membrane indicative of PKC activation, whereas TRP-14 had no effect at any concentration. TRP-14 at 100 microM desensitized BPAEC to thrombin-induced increases in [Ca2+]i and transendothelial permeability. The Ca2+ desensitization was reversed after approximately 60 min, and this recovery paralleled the recovery of the permeability response. These findings indicate that the TRP-14-induced Ca2+ mobilization in the absence of PKC activation is insufficient to increase endothelial permeability. In contrast, the increase in endothelial permeability after alpha-thrombin occurred in conjunction with Ca2+ mobilization as well as PKC activation. TRP-14 pretreatment prevented the alpha-thrombin-induced increase in endothelial permeability secondary to desensitization of the Ca2+ signal. The results suggest that combined cytosolic Ca2+ mobilization mediated by TRP-14 and PKC activation mediated by a TRP-14-independent pathway are dual signals responsible for the thrombin-induced increase in vascular endothelial permeability.

Amino Acid Sequence↗
PubMed1993

Albumin and Ricinus communis agglutinin decrease endothelial permeability via interactions with matrix.

We studied the effects of albumin and the lectin Ricinus communis agglutinin (RCA) on hydraulic conductivity (Lp) of bovine pulmonary microvascular endothelial cell monolayers (BPMVEC) because of the evidence that albumin and RCA can interfere with transendothelial albumin permeability (Siflinger-Birnboim, A., J. Schnitzer, H. Lum, F. Blumenstock, C. Shen, P. Del Vecchio, and A. Malik. J. Cell. Physiol. 149: 575-584, 1991). BPMVEC were seeded on microporous polycarbonate filters, and the liquid flux was measured by collecting effluent into a tubing of known inner diameter at transendothelial hydrostatic pressures (P) ranging from 5 to 20 cmH2O. Lp was calculated as the slope of the relationship of liquid flux per unit surface area (Jv) vs. P. Addition of RCA (50 micrograms/ml) or albumin (5 mg/ml) to the endothelial cell medium containing albumin-free Hanks' balanced saline solution (HBSS) decreased total Lp (expressed x 10(-6) cm.s-1 x cmH2O-1) from 17.2 +/- 3.6 during HBSS to 4.7 +/- 0.9 during albumin and 5.7 +/- 1.6 during RCA (P < 0.01 for both). The RCA effect, but not that of albumin, was prevented by the addition of D-galactose (0.1 M) (the cognate hapten monosaccharide of RCA). We determined the contribution of the extracellular matrix (ECM) in decreasing the Lp by obtaining ECM after treatment of the monolayers with 0.025 M NH4OH to detach endothelial cells from the ECM. Basal ECM Lp (expressed x 10(-6) cm.s-1 x cmH2O-1) was 57.0 +/- 15.3, and it decreased to 19.7 +/- 4.3 and 17.5 +/- 2.9 during RCA and albumin, respectively (P < 0.01 for both). In contrast, RCA and albumin did not alter the filter Lp values. Another lectin, Ulex europaeus agglutinin, and the protein immunoglobulin G had no effect on Lp values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Adenosine 3',5'-cyclic monophosphate attenuates neutrophil-mediated increase in endothelial permeability.

We studied the effects of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) and cholera toxin (CT) on 125I-labeled albumin flux across confluent monolayers of bovine pulmonary microvessel endothelial cells (BMVEC) grown on polycarbonate filters (10(5) BMVEC/filter). 8-BrcAMP and CT increased endothelial adenosine 3',5'-cyclic monophosphate (cAMP) concentrations about twofold. Polymorphonuclear leukocytes (PMN) were layered on BMVEC monolayers (ratio of 10:1) and activated with phorbol 12-myristate 13 acetate (PMA; 5 x 10(-9) M). Transendothelial 125I-labeled albumin clearance rate was measured to determine the endothelial permeability alterations. Activation of PMN in control monolayers resulted in an increase in transendothelial 125I-labeled albumin clearance rate from 0.090 +/- 0.011 to 0.37 +/- 0.06 microliters/min (P < 0.01). Treatment of endothelial monolayers with 8-BrcAMP (10(-3) M) significantly attenuated the increase in endothelial permeability after PMN activation (transendothelial 125I-labeled albumin clearance rate increased to 0.19 +/- 0.03 microliters/min; P < 0.01). Pretreatment of BMVEC monolayers with CT (10(-8) M) for 3 h before PMN activation prevented the PMN-mediated increase in endothelial permeability (125I-labeled albumin clearance rate only increased to 0.13 +/- 0.018 microliters/min). To simulate the effect of PMN activation, hydrogen peroxide (H2O2) was added directly onto BMVEC; both 8-BrcAMP and CT were shown to reduce the H2O2-mediated increase in endothelial permeability. 8-BrcAMP and CT pretreatment did not prevent PMN adhesion to BMVEC monolayer and superoxide anion and H2O2 production after PMA activation of PMN. We conclude that increased endothelial cAMP concentration prevents PMN-mediated endothelial injury by an action of the cyclic nucleotide on endothelial cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

Activation of protein kinase C pathway contributes to hydrogen peroxide-induced increase in endothelial permeability.

BACKGROUND: We examined the effects of hydrogen peroxide (H2O2) on endothelial permeability and the possible role of protein kinase C (PKC) activation in mediating the response. EXPERIMENTAL DESIGN: Pulmonary microvessel endothelial cell monolayers were grown to confluency on gelatin- and fibronectin-coated microporous filters. Endothelial permeability was measured by determining the transendothelial clearance rate of [125I]albumin. The monolayers in all cases were challenged for 1 hour with H2O2. In some experiments, the monolayers were preincubated with PKC inhibitors H7 (an isoquinolinylsulphonamide derivative) (0.05 mM) or calphostin C (5 x 10(-6) mM) or with the inactive isoquinolinylsulphonamide analog, HA1004 (0.05 mM), before the H2O2 challenge. RESULTS: Addition of H2O2 (0 to 0.5 mM) to endothelial monolayers in the absence of PKC inhibitors resulted in a concentration-dependent increases in endothelial permeability and the response occurred without LDH release and morphologic evidence of cytolysis. The increase in permeability was significantly reduced by H7 and calphostin C, but not by HA1007. Immunocytochemical localization of PKC indicated that PKC isotype II was abundant in these cells and that it was distributed uniformly in the cytosol. H2O2 induced translocation of PKC to the cell membrane indicating enzyme activation. H7 and calphostin C prevented the H2O2-induced PKC translocation, whereas HA1004 had no effect. Both PKC inhibitors also prevented cell "rounding" and formation of interendothelial gaps, whereas HA1004 was ineffective. CONCLUSIONS: The results indicate that PKC activation is an important determinant of the H2O2-induced increase in endothelial permeability.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Lectin binding to gp60 decreases specific albumin binding and transport in pulmonary artery endothelial monolayers.

The effect of albumin binding to cultured bovine pulmonary artery endothelial cell (BPAEC) monolayers on the transendothelial flux of 125I-labelled bovine serum albumin (BSA) was examined to determine its possible role on albumin transcytosis. The transport of 125I-BSA tracer across BPAEC grown on gelatin- and fibronectin-coated filters (0.8 microns pore diam.) was affected by the presence of unlabelled BSA in the medium in that transendothelial 125I-BSA permeability decreased, reaching a 40% reduction at BSA concentrations equal to or greater than 5 mg/ml. BSA binding to BPAEC monolayers was saturated at concentration of 10 mg/ml with an apparent binding affinity of 6 x 10(-7) M. In contrast, gelatin added to the medium altered neither 125I-BSA binding nor transport. Several lectins were tested for their ability to inhibit 125I-BSA binding and transport. One lectin, Ricinus communis (RCA), reduced 125I-BSA binding by 70% and transport by 40%. Other lectins, Ulex europaeus, Triticum vulgare, and Glycine max decreased neither 125I-BSA binding nor transport. The reduction of 125I-BSA transport by RCA was not observed in the presence of saturating levels of BSA, indicating that RCA influenced only the albumin-dependent component of transport. RCA, but not other lectins, precipitated a 60 kDa plasmalemmal glycoprotein from cell lysates of surface radioiodinated BPAEC monolayers. This 60 kDa glycoprotein appears to be the equivalent of gp60 identified previously as an albumin binding glycoprotein in rat microvascular endothelium. In summary, approximately 40% of albumin transport across BPAEC monolayers is dependent on albumin binding. This component of albumin transport is inhibited by 80% by the binding of RCA to gp60. These results suggest that binding of albumin to gp60 on pulmonary artery endothelial cell membrane is a critical determinant of transendothelial albumin flux involving mechanisms such as plasmalemmal vesicular transcytosis.

Animals↗
PubMed1991

Serum albumin decreases transendothelial permeability to macromolecules.

We examined the effects of serum albumin and other serum proteins on the fluxes of tracer 125I-albumin (MW 69 kDa) and 125I-haptoglobin (MW 100 kDa) across the pulmonary artery endothelial monolayer in vitro to test the role of serum proteins in modulating the endothelial barrier function. Replacement of control complete culture medium (20% fetal calf serum in DMEM) with DMEM alone increased the transendothelial 125I-albumin clearance rate (a measure of 125I-albumin permeability) by 83% of the control value. Repletion with 50% calf serum or with 2.0 g% albumin (i.e., the albumin concentration in 50% serum) decreased 125I-albumin permeability to the control value. This effect of serum or albumin was concentration-dependent since neither 12.5% serum nor 0.5 g% albumin (i.e., albumin concentration in 12.5% serum) altered 125I-albumin permeability from control values. The ammonium sulfate-precipitated serum protein fraction rich in albumin decreased 125I-albumin permeability from the control DMEM value, whereas serum fractions containing predominantly gamma-globulin or depleted of protein did not significantly alter 125I-albumin permeability. Other serum proteins that have been proposed to reduce endothelial permeability, alpha 1-acid glycoprotein (0.035-0.14 g/100 ml) and fibronectin (5 mg/100 ml), did not decrease 125I-albumin permeability from DMEM values. The endothelial permeability of 125I-haptoglobin of 4.63 +/- 0.53 x 10(-6) cm/sec in the presence of DMEM was 30% of the 125I-albumin permeability value. The addition of 2.0 g% albumin or 50% serum decreased 125I-haptoglobin permeability to 57 and 31%, respectively, of the DMEM value. These results indicate the critical role of serum albumin in regulating the restrictiveness of the endothelial barrier to macromolecules.

Animals↗
PubMed1988

Selectivity of the endothelial monolayer: effects of increased permeability.

We investigated the mechanism of thrombin-induced increases in endothelial monolayer permeability by examining the effect of thrombin on the molecular sieving characteristics of the endothelial monolayer and comparing the responses of arterial- and venous-derived endothelial cell lines. Bovine pulmonary artery (BPA) and pulmonary vein (BPV) endothelial cells were similarly harvested and cultured. The endothelial cells were grown to confluence on gelatinized polycarbonate filters and the permeabilities to sucrose, albumin, and IgG were measured and corrected for effects of unstirred layers. The control permeabilities of BPA and BPV were similar with both monolayers, demonstrating selectivity to different sized tracer molecules. alpha-Thrombin (10(-6) M) increased the permeability of both BPA and BPV to albumin and sucrose. The permeability of BPA was increased to a greater extent than BPV, perhaps due to phenotypic differences. In both cell lines, the permeability increase was most pronounced for albumin, which by pore theory is best described by an increase in the radius of the small pore pathway for diffusion.

Animals↗
PubMed1987

Molecular sieving characteristics of the cultured endothelial monolayer.

We examined the selectivity of the bovine pulmonary artery endothelial monolayer in vitro to molecules of different sizes. The cultured bovine pulmonary endothelial monolayer was grown on a gelatinized filter and the transendothelial transport was studied by determining the permeability of molecules ranging from 182 to 340,000 daltons under diffusion conditions. The permeabilities across the cultured bovine endothelium were modeled according to cylindrical pore theory. The data were best fit by a two-pore model with radii 65 A and 304 A and a ratio of small to large pores of 160:1. The results indicate that the cultured endothelial monolayer is a selective barrier to molecules of different sizes and that the molecular selectivity is consistent with a diffusional pathway through endothelial pore equivalents. The cultured endothelial monolayer is a useful system for studying the permeability characteristics of the endothelial barrier.

Animals↗
PubMed1987

Endothelial monolayer permeability to macromolecules.

The barrier function of the endothelial monolayer has not been extensively investigated using the cultured endothelium. The in vitro approach may contribute to a more complete understanding of microvessel wall permeability. Our studies using an in vitro endothelial monolayer system have led us to the following conclusions: the endothelial monolayer is more permeable to small-molecular-weight substances than to large molecules; the permeability of albumin is different for endothelial cells derived from different vascular sites (higher for pulmonary venous than pulmonary arterial endothelium); basement membrane components may have a significant role in the permeability of albumin across the endothelium; control of endothelial monolayer permeability is determined not only by the characteristics of the macromolecule (i.e., size and charge) but also by the shape of the endothelial cells and the size of interendothelial space.

Actins↗
PubMed1986

Thrombin-induced increase in albumin permeability across the endothelium.

We studied the effect of thrombin on albumin permeability across the endothelial monolayer in vitro. Bovine pulmonary artery endothelial cells were grown on micropore membranes. Morphologic analysis confirmed the presence of a confluent monolayer with interendothelial junctions. Albumin permeability was measured by the clearance of 125I-albumin across the endothelial monolayer. The control 125I-albumin clearance was 0.273 +/- 0.02 microliter/min. The native enzyme, alpha-thrombin (10(-6) to 10(-10) M), added to the luminal side of the endothelium produced concentration-dependent increases in albumin clearance (maximum clearance of 0.586 +/- 0.08 microliter/min at 10(-6) M). Gamma (gamma) thrombin (10(-6) M and 10(-8) M), which lacks the fibrinogen recognition site, also produced a concentration-dependent increase in albumin clearance similar to that observed with alpha-thrombin. Moreover, the two proteolytically inactive forms of the native enzyme, i-Pr2 P-alpha-thrombin and D-Phe-Pro-Arg-CH2-alpha-thrombin, increased the 125I-albumin clearance (0.610 +/- 0.09 microliter/min and 0.609 +/- 0.02 microliter/min for i-Pr2 P-alpha-thrombin and D-Phe-Pro-Arg-CH2-alpha-thrombin at 10(-6) M, respectively). Since the modified forms of thrombin lack the fibrinogen recognition and active serine protease sites, the results indicate that neither site is required for increased albumin permeability. The increase in albumin clearance with alpha-thrombin was not secondary to endothelial cell lysis because lactate dehydrogenase concentration in the medium following thrombin was not significantly different from baseline values. There was also no morphological evidence of cell lysis. Moreover, the increase in 125I-albumin clearance induced by alpha-thrombin was reversible by washing thrombin from the endothelium. The basis for the increased albumin permeability following the addition of alpha-thrombin appears to be a reversible change in endothelial cell shape with formation of intercellular gaps.

Animals↗
PubMed1986

Transendothelial albumin flux: evidence against asymmetric transport.

We examined the recent proposition (Circ. Res. 57: 903-905, 1985) that the interstitium-to-luminal transport of albumin is an active phenomenon. Studies were made using cultured bovine and sheep pulmonary-artery endothelial cells. The transendothelial 125I-albumin flux from the luminal-to-abluminal side was compared with the flux from the abluminal-to-luminal side. The endothelial cells were grown to confluence on gelatinized-polycarbonated filters separating the abluminal from the luminal compartments. The albumin concentration in each compartment was 1 g/100 ml to equalize the oncotic pressure gradients. The effect of hydrostatic pressure was eliminated by maintaining equal fluid levels in both compartments. The transendothelial albumin flux across the monolayer was measured by adding the 125I-albumin tracer either on the luminal or the abluminal side. A double-isotope method was also used to study bidirectional transendothelial flux of albumin at the same time for the same cultured endothelium. The results indicated that albumin flux from the luminal-to-abluminal side was equal to the flux from the abluminal-to-luminal side. Both bovine and sheep pulmonary artery endothelial cells in culture behave symmetrically for albumin, suggesting that albumin is not actively transported from the interstitium to the lumen.

Animals↗
PubMedDate not supplied

Culture and characterization of pulmonary microvascular endothelial cells.

Surface proteins were compared in endothelial cells (EC) obtained from bovine peripheral lung, pulmonary artery and vein, and dorsal aorta using sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. Galactose-containing glycoproteins [molecular weight (M(r)) 160-220 and 40 kDa] binding to the Ricinus communis agglutinin (RCA) and peanut agglutinin (PNA) were selectively observed on pulmonary microvessel EC as compared to EC from pulmonary artery, pulmonary vein, and dorsal aorta. The unique RCA- and PNA-binding profiles of EC from the pulmonary artery and microvessels may be important in characterizing EC from different sites in the pulmonary circulation. The pulmonary microvessel EC monolayer was also 15-fold more restrictive to transendothelial flux of [14C]sucrose (M(r) = 342 Da) than the pulmonary artery EC monolayer. In contrast, the microvessel EC were only six- and twofold more restrictive to the flux of larger tracer molecules, ovalbumin (M(r) 43 kDa) and albumin (M(r) = 69 kDa) than pulmonary artery EC. The greater restrictiveness of pulmonary microvessel EC monolayer indicates a major phenotypic difference in the cultured pulmonary microvessel EC barrier function.

Animals↗