Location of focal silver staining at endothelial gaps in inflamed venules examined by scanning electron microscopy. Hirata, Akira, Peter Baluk, Takashi Fujiwara, and Donald M. McDonald. Cardiovascular Research Institute and Department of Anatomy, University of California, San Francisco, CA 94143, Present address: Department of Anatomy and Ophthalmology, Kumamoto University School of Medicine, Kumamoto 860, JAPAN, Present address: Laboratory Animal Center, Ehime University School of Medicine, Shigenobu, Ehime 791-02, JAPAN
APStracts 2:0077L, 1995.
The century-old histological technique of silver nitrate staining has proven to be extremely useful for visualizing endothelial cell borders and localizing endothelial gaps, but the significance of the staining is still not fully understood. To gain some insight into what silver nitrate stains, we developed a method that enabled us to use scanning electron microscopy with backscattered and secondary electron imaging to examine silver staining at endothelial cell borders of venules of the rat tracheal mucosa. We found that in normal venules, silver lines followed the smooth contour of cell borders. However, 1 min after endothelial permeability was increased by substance P, cell borders were irregular and displaced from the silver lines by as much as 4.3 [mu]m, and the lines were accompanied by three types of silver deposits. Most common (46% of total) were annulus-shaped silver deposits that surrounded endothelial gaps. These deposits averaged 1.5 [mu]m in width, were positioned symmetrically across cell borders, and were located at a depth of 0.3 [mu]m beneath the luminal surface. Many endothelial gaps were partitioned into multiple pores (mean, 2.4) by finger-like processes of endothelial cells. Surprisingly, the gaps occupied only 5.4% of the total area of the silver deposits and constituted 0.15% of the luminal surface of the leaky postcapillary venules. A second type of silver deposit ( 19% of total) was positioned asymmetrically with respect to the cell border and marked sites where endothelial cell margins still overlapped but appeared to be vertically separated by obliquely-oriented gaps. A third type marked gaps at 3-cell junctions; these were no more abundant than deposits elsewhere around the cell perimeter, suggesting that 3-cell junctions were not unusually leaky sites. We conclude that silver nitrate marks endothelial cell borders and outlines endothelial cell gaps by staining an element of intercellular junctions. The annular shape of many silver deposits around gaps suggests that junctional elements in the apposing cells are separated during gap formation but are still present at the gap perimeter.

Received 14 November 1994; accepted in final form 1 May 1995.
APS Manuscript Number L326-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  9 May 1995.