Different kinds of polypeptides and polypeptide-coated nanoparticles are accepted by the selective transcytosis shown in the rabbit nasal mucosa

Abstract

The specific transcytosis of polypeptides, demonstrated in the nasal respiratory mucosa of the rabbit, seems to be involved in antigen sampling at the airway entry, since absorption has been shown only to occur if lymphoid aggregates are present beneath the epithelium and to be proportional to aggregate volume. Nanoparticles and many polypeptides besides the two previously tested (i.e. carbocalcitonin (CCT) and adrenocorticotropic hormone) should be transportable, in agreement with the vesicular transcytosis and antigen sampling hypothesis. Thus unidirectional mucosa-submucosa and opposite fluxes ( J ms, J sm) and the corresponding net fluxes ( J net) of uncoated or polypeptide-coated polystyrene nanospheres (diameter: about 0.5 μm) have been measured with the aid of spectrophotometry and quantitative dark-field microscopy. No net transport has been observed for uncoated beads, whereas it has always been shown for polypeptide-coated beads, although to different extents. The selectivity sequence for the polypeptides tested is as follows: BSA≅enkephalin≪anti-BSA IgG≅IgA≅CCT≅insulin≤anti-insulin IgG. With the exception of BSA and enkephalin-coated beads, whose J net is very small, in all the other cases the apparent affinities for receptors seem to be equal or similar; just over 6% polypeptide coating on the nanosphere is sufficient to elicit maximal transport; finally, transport seems to require many cooperating binding sites between the single nanosphere and receptors or one or many non-cooperating binding sites, but with a threshold number of polypeptide molecules adsorbed on the nanosphere to reach a minimal binding probability.