Passive Sensitization and Antigen Challenge Increase Vascular Permeability in Rat Airways

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Abstract
Activation of mast cells in all organs in which this phenomenon has been studied leads to increased vascular permeability. Mucosal edema is thought to be an important component of the airflow obstruction of asthma. In order to develop a model to study IgE-mediated vascular permeability in lung, rats were passively sensitized with a murine monoclonal IgE-anti-dinitrophenyl (DNP). Forty-eight hours later, the animals were challenged intravenously with mouse serum albumin conjugated to DNP (1 to 25 .mu.g) and received 125I-labeled bovine albumin at the same time to permit assessment of leakage of vascular proteins into the lungs. The animals became cyanotic, but they did not die. Control animals were challenged with mouse serum albumin alone and experienced no systemic reactions. The trachea, the hilum, and peripheral lung were removed and the radioactivity determined. Compared to control animals, vascular permeability was increased most impressively in the trachea and to a lesser extent in the hilum. No increased vascular permeability was found in the peripheral lung. In dose-response experiments (1 to 25 .mu.g MSA-DNP injected), the peak effect in the trachea occurred at 25 .mu.g MSA-DNP (+ 450 .+-. 119% above control values, p .ltoreq. 0.05), while the response in the bronchus was less dose dependent; maximal increase above control was at 12.5 .mu.g DNP-MSA (+ 50 .+-. 8%, p .ltoreq. 0.05). The increased plasma exudation in the trachea and bronchi peaked within 5 min of antigen challenge and remained significantly increased for at least 2 h. After 8 h, no increased radioactivity could be observed. To understand the reason for the regional response to anaphylaxis in rat lung, the distribution of mast cells was delineated. Mast cells were found in the trachea in the intercartilaginous regions and in the bronchial walls, most notably around the small vessels and in the adventitia of large vessels. No mast cells were found in the interalveolar walls. In close correspondence to this histologic data, the histamine content of the trachea was 20.8 .+-. 1.2 ng/ml wet weight, while the mainstem bronchus contained 13.0 .+-. 1.0 ng. The peripheral lung was found to contain only 3.6 .+-. 0.3 ng (p < 0.001 compared to either trachea or hilum). Thus, anaphylaxis of rat lung caused increased regional vascular permeability occurring only in the areas rich in mast cells (trachea, bronchi) while having no effect on vascular permeability in the relatively mast cell-free alveolar walls.