Modulation of microvessel wall charge by plasma glycoprotein orosomucoid

Abstract

Haraldsson and Rippe suggested that the circulating glycoprotein orosomucoid (alpha 1-acid glycoprotein) contributes to the net charge on microvessel walls (Acta Physiol. Scand. 129: 127-135, 1987). We tested their hypothesis in individually perfused microvessels of frog mesentery by measuring solute permeability coefficients of two globular proteins (alpha-lactalbumin and ribonuclease) having approximately the same size (Stokes radius, 2 nm) but different charge (-11 and +3, respectively). In vessels perfused with orosomucoid (0.1 and 1 mg/ml) in a Ringer-albumin perfusate, the solute permeability coefficient of alpha-lactalbumin decreased to one-half [0.47 +/- 0.25 (SD)] the value in the absence of orosomucoid, and the solute permeability coefficient of ribonuclease was close to six times as large as alpha-lactalbumin permeability. Both results may be accounted for if orosomucoid increases the net negative charge on microvessel walls in frog mesentery from 11.2 to 28 meq/l. A similar change in microvessel charge would be more than sufficient to account for the decrease in albumin clearance in the presence of orosomucoid reported by Haraldsson and Rippe in rat muscle microvessels.

True

“…The charge-dependence in vascular permeability in tumours is consistent with observations in normal tissues (Jain, 1997;Curry et al, 1987;Turner et al, 1983;Vehaskari et al, 1984;Deen et al, 1980;Baldwin et al, 1991;Dermietzel et al, 1983;Adamson et al, 1988;Barrowcliffe et al, 1990;Gandhi and Bell, 1992;Gilchrist and Parker, 1985;Haraldsson et al, 1983;Khaw et al, 1991;Leypoldt and Henderson, 1993;Michel and Phillips, 1985;Öjteg et al, 1987;Parker et al, 1985;Rasio and Goresky, 1985;Triguero et al, 1989), suggesting the luminal surface of tumour vascular endothelium is negatively charged as well.…”

“…Thus, it restricts the extravasation of anionic macromolecules, as has been demonstrated in cultured endothelial cell monolayer (Sahagun et al, 1990) and various normal tissues (Jain, 1997;Curry et al, 1987;Turner et al, 1983;Vehaskari et al, 1984;Deen et al, 1980;Baldwin et al, 1991;Dermietzel et al, 1983;Adamson et al, 1988;Barrowcliffe et al, 1990;Gandhi and Bell, 1992;Gilchrist and Parker, 1985;Haraldsson et al, 1983;Khaw et al, 1991;Leypoldt and Henderson, 1993;Michel and Phillips, 1985;Öjteg et al, 1987;Parker et al, 1985;Rasio and Goresky, 1985;Triguero et al, 1989). Adamson et al (1988) have demonstrated that the microvascular permeability to α-lactalbumin (M r = 14 176, net charge -10) is approximately 50% of that to ribonuclease (M r = 13 683, net charge +4), suggesting that the microvascular permeability to the positively charged molecules is higher than the permeability to the negative ones.…”

“…In normal tissues, the luminal endothelial membrane is negatively charged (Curry et al, 1987;Turner et al, 1983;Vehaskari et al, 1984;Deen et al, 1980;Baldwin et al, 1991;Dermietzel et al, 1983). Thus, it restricts the extravasation of anionic macromolecules, as has been demonstrated in cultured endothelial cell monolayer (Sahagun et al, 1990) and various normal tissues (Jain, 1997;Curry et al, 1987;Turner et al, 1983;Vehaskari et al, 1984;Deen et al, 1980;Baldwin et al, 1991;Dermietzel et al, 1983;Adamson et al, 1988;Barrowcliffe et al, 1990;Gandhi and Bell, 1992;Gilchrist and Parker, 1985;Haraldsson et al, 1983;Khaw et al, 1991;Leypoldt and Henderson, 1993;Michel and Phillips, 1985;Öjteg et al, 1987;Parker et al, 1985;Rasio and Goresky, 1985;Triguero et al, 1989).…”

Effect of Surface Charge of Immortalized Mouse Cerebral Endothelial Cell Monolayer on Transport of Charged Solutes

“…29,35 Orosomucoid is also bound to the surface of cultured bovine pulmonary microvascular endothelial cells. 36 It has been found that orosomucoid modulates the transport of charged solutes across the wall of peripheral and cerebral microvessels in vivo by decreasing the transport of negatively charged molecules but increasing that of positively charged ones, 13,23,46 suggesting that orosomucoid plays an essential role in maintaining the permeability property of endothelium by adding negative charge to the SGL. 13,23,38 The second objective of the present study is thus to investigate whether orosomucoid modulates the bEnd3 monolayer permeability in a similar way as it does for the intact endothelium of the BBB.…”

Adipocytokine Orosomucoid Integrates Inflammatory and Metabolic Signals to Preserve Energy Homeostasis by Resolving Immoderate Inflammation

“…Consistently, injection of exogenous ORM protects mice from TNF␣-induced lethality (18). Additionally, it has been proposed that ORM changes the polyanionic charge selectivity of capillary walls, and thereby plays the role of a barrier for capillary permeability (19,20). Another interesting feature of ORM is associated with its structure.…”