How early studies of inflammation led to our current views on the roles of vascular adhesion molecules

Abstract

Dutrochet [1] is generally credited with the first observation, in 1824, that leukocytes could be seen to emigrate across the walls of small blood vessels, and the experimental induction of leukocyte diapedesis in response to tissue injury was first reported by Addison in 1843 [2]. The most elegant early experimental studies were carried out by Arnold in Heidelberg in the 1870s, examining leukocyte adhesion to, and demonstrating emigration between, endothelial cells in small blood vessels of the frog [3, 4]. He used silver staining to outline endothelial cell boundaries, and injection of cinnabar to detect sites of leakage. The resulting drawings (e.g. Fig. 1) accurately demonstrate the early stages of the acute inflammatory process in as much detail as many contemporary textbooks. He was also perspicacious enough to attribute emigration to a molecular process, writing: “It is possible that chemical agents seep into interendothelial junctions and thereby attract pavemented leukocytes, but there is, as yet, no evidence for this concept”.