Allergen challenge-induced extravasation of plasma in mouse airways.
BACKGROUND
Mouse models are extensively used to study genetic and immunological mechanisms of potential importance to inflammatory airway diseases, e.g. asthma. However, the airway pathophysiology in allergic mice has received less attention. For example, plasma extravasation and the ensuing tissue-deposition of plasma proteins, which is a hallmark of inflammation, has not been examined in allergic mice.


OBJECTIVE
This study aims to examine the vascular permeability and the distribution of plasma proteins in mouse airways following exposure to allergen and serotonin.


METHODS
Extravasated plasma was quantified by a dual isotop technique using intravascular (131I-albumin) and extrasvascular (125I-albumin) plasma tracers. Histological visualization of fibrinogen and colloidal gold revealed the tissue distribution of extravasated plasma.


RESULTS
Allergen aerosol exposure (3% OVA, 15min) of sensitized animals resulted in a marked plasma extravasation response in the trachea (P < 0.01) and the bronchi but not in the lung parenchyma. A similar extravasation response was induced by serotonin (P<0.001). Extravasating vessels (assessed by Monastral blue dye) were identified as intercartilaginous venules. Extravasated plasma abounded in the subepithelial tissue but was absent in the epithelium and airway lumen. The allergen-induced response was dose-dependently inhibited by iv administration of formoterol (P < 0.001), a vascular antipermeability agent.


CONCLUSIONS
The present study demonstrates that serotonin and allergen challenge of sensitized mice increase airway venular permeability to cause transient extravasation and lamina propria distribution of plasma in the large airways. We suggest that the extravasation response is a useful measure of the intensity and the distribution of active inflammation
Department of Physiology and Neuroscience, University Hospital, Lund, Sweden.
J S
JS
Erjefält
P
P
Andersson
B
B
Gustafsson
M
M
Korsgren
B
B
Sonmark
C G
CG
Persson
D000336:Aerosols; D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D001980:Bronchi / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability / Q000276:immunology*; D004983:Ethanolamines / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D000068759:Formoterol Fumarate; D017979:Gold Colloid; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014132:Trachea / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology
D000336:Aerosols; D000485:Allergens; D001798:Blood Proteins; D004983:Ethanolamines; D017979:Gold Colloid; D012702:Serotonin Antagonists; D012701:Serotonin; D005340:Fibrinogen; D010047:Ovalbumin; D000068759:Formoterol Fumarate