© 2006 American Thoracic Society
Periarterial Leukocyte Accumulation in Allergic Airway InflammationFrom the Authors:Dr. Pabst has pointed out the importance of the periarterial space in the lung during inflammatory and allergic reactions. In our study (1), intranasal administration of adeno-UGRP1 successfully led to high levels of UGRP1 expression in the epithelial cells of the respiratory tract in ovalbumin-induced allergic airway inflammation in mice, resulting in effective suppression of airway inflammation. In particular, this was characterized by the absence of infiltrating eosinophils in their lungs. Dr. Pabst suggests that this finding is likely due to diffusion of epithelial cell–derived UGRP1 protein into the periarterial space where leukocytes infiltrate. If, in fact, UGRP1 diffuses into the periarterial space, one would expect a gradient with the highest concentration at the epithelial surface, which then tapers off with increased distance away from the epithelium. By immunohistochemistry, we did not find any UGRP1 expression in areas in the respiratory tract other than epithelial cells. However, this does not exclude the possibility that UGRP1 diffuses from the epithelium toward the periarterial space. This may simply be due to the sensitivity of the antibody used. In particular, UGRP1 may have a different structure after secretion, such as being in a polymeric form or bound to a carrier protein, which may render the antibody less sensitive. Provided UGRP1 diffuses, how far the protein can reach and how much of it is required to suppress inflammation are other questions that have to be addressed. Alternatively, UGRP1 may function as a signaling molecule to which neighboring cells respond, and may produce a paracrine effect, resulting in suppression of inflammation, including blockade of infiltrating eosinophils. We currently do not have data to provide answers to these questions. Regarding the labeling in the figures, "v" for "vein" in Figures 1 and 3 and the structure in the upper right corner of Figure 5C labeled as "bronchus" should actually be labeled "vessels," as Dr. Pabst pointed out. To address the aforementioned questions and whether UGRP1 plays any role in the periarterial space relative to its role in allergic and/or inflammatory immune reactions of the lung, we must first understand the mechanism by which UGRP1 suppresses inflammation. Further study of this unique secretory protein could provide a new direction in understanding allergy and inflammation of the lung.
National Cancer Institute, National Institutes of Health Bethesda, Maryland FOOTNOTES Conflict of Interest Statement: Neither author has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
