the study by Lim et al., one of this issue's articles in focus (Ref. 6a, see p. L959), provides important new information on the potential use of intravital microscopy in evaluating the inflammatory response in postcapillary venules of the rat trachea. The pulmonary, mesentery, cheek pouch, and renal blood vessels have been studied for many years using this technique, but this is the first paper using intravital microscopy to study inflammation in the airway circulation.
The inflammatory response in the lung's circulation has been extensively studied using biophysical measures of endothelial damage and incorporating immunological techniques to evaluate the role of cytokines as well as plasma and tissue cells involved in producing the ischemia-reperfusion injury of microvessels in isolated or in situ lungs (1, 9). Ischemia-reperfusion has been and still remains an important model to evaluate and define the inflammatory system when either the lung or other organs, remote from the lung, are subjected to periods of ischemia and the resulting inflammatory response in the lung evaluated following reperfusion (2, 4). It is well known that asthma is an inflammatory disease associated with airway smooth muscle, yet it has been extremely difficult to study the airway circulation's contribution to the tissue accumulation of neutrophils, monocytes, and their release of inflammatory mediators in asthma. An experimental model that can evaluate inflammation in the airway circulation will prove to be an extremely useful addition to our experimental inflammation model repertoire.
The present study clearly shows that the airway circulation can be studied in inflammation caused by challenges with eitherN-formyl-methionyl-leucyl-phenylalanine or lipopolysaccharide, and the mechanisms responsible for producing the inflammation were evaluated in a quantitative fashion. Although the inflammatory response in airways is well defined in asthma (3,8), and the inflammatory response to interleukin-1β and tumor necrosis factor-α, important inflammatory cytokines, has also been studied in isolated airway smooth muscle cells (7), the paper by Lim et al. (6a) is the first to use intravital microscopy. There is absolutely no doubt that the techniques presented by Lim et al. provide a new model in which the inflammatory response can be evaluated in the airway circulation relative to monocyte and neutrophil activation, infiltration of leukocytes into the tissues, and the ways by which various cytokines and chemokines are involved in the phenomena. The airway circulation's response to inflammation is definitely an area in need of new techniques, and we believe that Lim et al. provide a new and valuable method in a research area that has previously relied on either histological or tissue staining techniques to define inflammatory responses in the airways.
Although Landis et al. (6) popularized the mesentery technique to evaluate capillary filtration in the 1930s as they worked in Krogh's laboratory, their technique has been used to provide substantial new information about the inflammatory response in many organs over the last decade (5). Applying these same experimental principles to the airway circulation will greatly extend our knowledge of the airway circulation and provide the necessary information to understand the mechanisms involved in the airway inflammatory process. We can hardly wait to see the data resulting from this technique to evaluate the inflammatory responses in the airway circulation, not just with ischemia-reperfusion but also with the evaluation of experimental rhinitis and the effect of various oligonucleotides and dust mite allergies on the airway microcirculation. Future studies using the techniques outlined by Lim et al. may allow us not only to open the black box of asthma development in the airways but also to accelerate the development of new therapies to use in patients subjected to various forms of inflammation. For the first time we will be able to observe how neutrophils roll, adhere, and migrate across the airway endothelial barrier during inflammation. The time course of various monocytes adhering in the process can also be evaluated in response to challenges with various cytokines and chemokines and their specific antibodies in portions of the airway circulation under study. There is absolutely no doubt that this technique will be rapidly adapted to determine the mechanisms associated with the inflammatory response because it definitely provides quantitative assessments of how various inflammatory cells respond in the airway circulation during a defined inflammatory stress.
Address for reprint requests and other correspondence: A. E. Taylor, Dept. of Physiology, College of Medicine, Univ. of South Alabama, Mobile, AL 36688 (E-mail:).
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