MOLECULAR HETEROGENEITY OF THE VASCULAR ENDOTHELIUM REVEALED BY IN-VIVO PHAGE DISPLAY

Vascular beds are known to differ in structure and metabolic function, but less is known about their molecular diversity. We have studied or gan-specific molecular differences of the endothelium in various tissu es by using in vivo screening of peptide libraries expressed on the su rface of a bacteriophage. We report here that targeting of a large num ber of tissues with this method yielded, in each case, phage that home d selectively to the targeted organ. Different peptide motifs were rec overed from each of these tissues. The enrichment in homing to the tar get organs relative to an unselected phage was 3-35-fold. Peptide sequ ences that conferred selective phage homing to the vasculature of lung , skin, and pancreas were characterized in detail, Immunohistochemistr y showed that the phage localized in the blood vessels of their target organ. When tested, the phage homing was blocked in the presence of t he cognate peptide. By targeting several tissues and by showing that s pecific homing could be achieved in each case, we provide evidence tha t organ- and tissue-specific molecular heterogeneity of the vasculatur e is a general, perhaps even universal, phenomenon. Our results also s how that these molecular differences can serve as molecular addresses.