The effect of human eosinophil granule major basic protein on airway responsiveness in the rat in vivo. A comparison with polycations.
Major basic protein (MBP) is a highly cationic protein found in the granules of eosinophils. It has been postulated that MBP may participate in the pathogenesis of airway hyperresponsiveness exhibited by asthmatic patients. Accordingly, we used a rat model to investigate the effect of human MBP instillation on airway responsiveness and the possible role of cationic charge in the determination of this effect. Dose-response characteristics to inhaled methacholine (MDRC) were determined at baseline, and the animals were allowed to recover. Then animals in the experimental group received 100 micrograms of purified human MBP via direct instillation into the trachea. One hour after instillation, the MDRC were again assessed. Control animals received (in lieu of MBP) buffer from the void volume pool of the same chromatography column used to purify the MBP. One hour after instillation of MBP there was a significant increase in airway responsiveness to inhaled methacholine, whereas control animals exhibited no increase in airway responsiveness. Some animals from the MBP group were restudied 48 h after MBP instillation, by which time airway responsiveness had returned to baseline level. The effect of the polycations poly-L-arginine and poly-L-lysine on airway responsiveness was also examined. As with MBP, airway responsiveness to inhaled methacholine increased 1 h after the instillation of either polycation. In addition, acetylation of the charged groups on poly-L-lysine resulted in a loss of this effect. Histologic examination of the airways failed to reveal airway epithelial shedding 1 h after MBP or polycation instillation.(ABSTRACT TRUNCATED AT 250 WORDS)
Uchida
D A
DA
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado.
Ackerman
S J
SJ
Coyle
A J
AJ
Larsen
G L
GL
Weller
P F
PF
Freed
J
J
Irvin
C G
CG
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D002412:Cations; D004305:Dose-Response Relationship, Drug; D047091:Eosinophil Granule Proteins; D005260:Female; D008168:Lung / Q000187:drug effects / Q000473:pathology; D016210:Methacholine Chloride / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011107:Polylysine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012260:Ribonucleases
D001798:Blood Proteins; D002412:Cations; D047091:Eosinophil Granule Proteins; D010455:Peptides; D016210:Methacholine Chloride; C080529:N-acetyl polylysine; D011107:Polylysine; C015462:polyarginine; D012260:Ribonucleases