Passive sensitization and antigen challenge increase vascular permeability in rat airways.
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 micrograms) 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 micrograms MSA-DNP injected), the peak effect in the trachea occurred at 25 micrograms MSA-DNP (+450 +/- 119% above control values, p less than or equal to 0.05), while the response in the bronchus was less dose dependent; maximal increase above control was at 12.5 micrograms DNP-MSA (+50 +/- 8%, p less than or equal to 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Sertl
K
K
Allergic Diseases Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Kowalski
M L
ML
Slater
J
J
Kaliner
M A
MA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D002199:Capillary Permeability; D004140:Dinitrophenols / Q000276:immunology; D007116:Immunization, Passive; D008168:Lung / Q000166:cytology; D008297:Male; D008407:Mast Cells / Q000166:cytology; D011652:Pulmonary Circulation; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000276:immunology; D014132:Trachea / Q000098:blood supply*
D000911:Antibodies, Monoclonal; D000941:Antigens; D004140:Dinitrophenols; D012709:Serum Albumin; C058064:dinitrophenyl-human serum albumin conjugate