ACTIVE-TRANSPORT OF POLYPEPTIDES IN RABBIT NASAL-MUCOSA - POSSIBLE ROLE IN THE SAMPLING OF POTENTIAL ANTIGENS

Transepithelial pathways of macromolecule transport have been studied in vitro in rabbit nasal respiratory mucosa, maintained at 27-degrees-C. Transepithelial electrical potential difference, short-circuit current and resistance were 3.4 +/- 0.5 mV (submucosa positive), 65.0 +/- 6.7-mu-A cm-2 and 52.1 +/- 5.6-OMEGA-cm-2 respectively (n = 15). These electrical characteristics are those of a leaky epithelium allowing macromolecules to permeate paracellularly. A detailed permeation study of a polypeptide (elcatonin, M(w) = 3362) was also undertaken. Elcatonin mucosa-submucosa (J(ms)) and submucosa-mucosa (J(sm)) fluxes were measured by radioimmunoassay. With 10-mu-g/ml elcatonin, J(ms) was significantly larger than J(sm) for the whole 120-min period of observation; net flux showed a maximum in the first 30 min (J(ms) = 13.6 +/- 1.0 ng cm-2 h-1, J(sm) = 1.4 +/- 0.1 ng cm-2 h-1, n = 10). J(ms) fell towards the value of J(sm) if the temperature was reduced to 4-degrees-C or if the mucosa was simultaneously treated with 0.1 mM dinitrophenol and 3 mM monoiodoacetate. J(ms) and J(net) followed saturation kinetics with increasing elcatonin concentrations. Adrenocorticotropic hormone (M(r) = 4500) produced a similar pattern to elcatonin. However, J(ms) and J(sm) were not significantly different from each other at any time either for [H-3]sucrose (M(w) = 342) or for [C-14]polyethyleneglycol-4000 (M(w) = 4000) when present in the bathing medium at 500-mu-M concentration. The results show active transport of polypeptides in parallel with passive permeation (possibly through leaky intercellular junctions). Active transport does not appear to be related to nonspecific pinocytosis but to receptor-mediated endocytosis. The latter may be important for the sampling of potential antigens from the nasal lumen.