A factor in serum lowers resistance and opens tight junctions of MDCK cells

Abstract

During an inflammatory reaction, factors in blood affect the permeability of endothelium and possibly organ epithelium. In this study we partially characterized a factor in human and canine blood that lowered the transepithelial electrical resistance (TER) of canine kidney epithelial cells (MDCK) and examined whether vascular permeability factors [complement component C3a and C5a and platelet-activating factor (PAF)] were responsible for this reaction. C3a and C5a caused a small (10-13%) dose-related decrease in the TER (alpha = 0.05), whereas PAF had no effect. In contrast, the factor found in both serum and plasma caused a large (60-83%) dose-dependent decrease (saturated at 30%) in the TER that was reversible within 60 min. The blood factor, which does not appear to be albumin, was heat stable and has an apparent molecular mass of 67 kDa. It preferentially decreased the TER of the epithelium when it came in contact with its basolateral surface and significantly lowered the resistance within 60 min by opening the zonula occludentes. These findings suggest that C3a, C5a, and a factor in blood can directly modulate the permeability of renal epithelium.

Serum Opens Tight Junctions and Reduces ZO‐1 Protein in Retinal Epithelial Cells

“…The two epithelial cell types also differ in terms of surface specificity of the serum effect. The effect on MDCK cells is specific for the basal surface (Conyers et al, 1990;Marmorstein et al, 1992), whereas that on the retinal epithelial cells is apical surface-specific. This latter difference probably reflects the reversal of surface polarity in the RPE cells as compared with kidney and other peripheral epithelial cell types (Junqueira et al, 1989;Rizzolo and Li, 1993).…”

“…In MDCK cells, serum induces a rapid decrease in resistance levels and the response reaches its peak within 40 min (Conyers et al, 1990) as compared with many hours for the RPE cells. The tight junction breakdown in MDCK cells is characterized structurally by focal condensation of the perijunctional actin ring at sites where three or more cells are in contact, whereas the actin microfilaments in the serum-treated RPE cells are not altered.…”

Mechanisms of alveolar protein clearance in the intact lung

“…For example, the previous section mentions possible benefits of reversing the procoagulant state in the alveolar space. Other potential therapies include proteins and peptides that open tight junctions for small solutes and macromolecules (18,44,51). Such agents could be investigated for their ability to speed alveolar protein clearance, although opening tight junctions could slow liquid clearance by allowing back flow into the air spaces.…”

Hydraulic Conductivity of Smooth Muscle Cell-Initiated Arterial Cocultures

“…E-MEM was added above and below the Transwell insert culture to eliminate the development of an osmotic pressure gradient. Fluid flux (J v ) across Transwell insert cultures in response to a transmembrane pressure differential of ΔP = 10 cmH 2 O was measured in pairs with a bubble tracking apparatus described previously [25] , and those measurements were used to calculate L p using equation (1). …”