Active transport of polypeptides in rabbit nasal mucosa: possible role in the sampling of potential antigens

Abstract

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 microA 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, Mw = 3362) was also undertaken. Elcatonin mucosa-submucosa (Jms) and submucosa-mucosa (Jsm) fluxes were measured by radioimmunoassay. With 10 micrograms/ml elcatonin, Jms was significantly larger than Jsm for the whole 120-min period of observation; net flux showed a maximum in the first 30 min (Jms = 13.6 +/- 1.0 ng cm-2 h-1, Jsm = 1.4 +/- 0.1 ng cm-2 h-1, n = 10). Jms fell towards the value of Jsm 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. Jms and Jnet followed saturation kinetics with increasing elcatonin concentrations. Adrenocorticotropic hormone (Mr = 4500) produced a similar pattern to elcatonin. However, Jms and Jsm were not significantly different from each other at any time either for [3H]sucrose (Mw = 342) or for [14C]polyethyleneglycol-4000 (Mw = 4000) when present in the bathing medium at 500 microM 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.(ABSTRACT TRUNCATED AT 250 WORDS)