Previous animal studies have demonstrated that following systemic administration phosphorothioate oligodeoxynucleotides (S-ODNs) are primarily excreted by the kidneys and that renal tissue levels of S-ODNs exceed that of other organs. Thus, the kidney may be an ideal target organ for application of antisense S-ODNs in vivo. We examined which cells within the rat kidney have uptake of radiolabeled S-ODNs following intravenous infusion. A 20-base ³⁵S-ODN was infused into 6 adult male Wistar rats. Three animals each were sacrificed 30 min and 4 h after infusion. The kidneys were then removed, fixed, and tissue autoradiography was performed. Similar results were obtained in both groups. The highest level of radioactivity was seen within the proximal tubules. Lower levels of activity were seen within the glomerulus, the parietal epithelial cells of Bowman’s space, and distal tubular cells. Very weak activity was also detected within the cells of the loop of Henle and the medullary collecting ducts. These results demonstrated that within the kidney S-ODNs were taken up primarily by proximal tubular cells, with much lower uptake by cells in other segments of the nephron.

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Monocyte adherence to endothelial or extracellular matrices plays an important role in triggering monocyte activation in extravascular sites of infection, chronic inflammatory disorders, and tissue damage. Migration of monocytes in the tissues involves the response to a chemoattractant and movement by a series of attachments and detachments to the extracellular matrices which are regulated by expression and distribution of specific receptors for the matrix proteins such as fibronectin (FN). The VSAs (very late antigens or beta integrins), a subfamily of the transmembrane heterodimeric integrin receptors, have been thought to play a major role in monocyte adherence to the extracellular matrices and cells. In this subfamily, VLA-5 and VLA-4 are believed to be the most essential integrins mediating monocyte adherence to FN. In the present report, we have established and compared different procedures for morphological evaluation of the expression and distribution of the FN receptors on human monocytes in order to investigate their response to endotoxin or cytokine stimulation.