Virus-induced airway hyperresponsiveness in guinea pigs in vivo: study of broncho-alveolar cell number and activity.
Recently, we demonstrated that an increased airway responsiveness in vitro can be measured 4, 8, and 16 days, but not 2 days, after intratracheal inoculation of parainfluenza-3 (PI-3) virus to guinea pigs. In the present study airway responsiveness was measured in vivo, and the number, types and activity of broncho-alveolar cells was determined. A significant increase in airflow resistance was measured in spontaneously breathing anesthetized guinea pigs in response to histamine and methacholine, 4 and 8 days after PI-3 virus inoculation. 2 days after inoculation with control solution or PI-3 virus, no difference in the total number of inflammatory cells was observed in the broncho-alveolar lavage fluid. In contrast, on days 4, 8, and 16 after infection a significant increase in the number of alveolar macrophages (102%, 76%, 68%, respectively), monocytes (552%, 374%, 360%, respectively), and lymphocytes (253%, 675%, 396%, respectively) was found. The number of eosinophils was increased as well, but faded with time (378%, 312%, 63%, respectively). PI-3 virus was found to be a very potent activator of broncho-alveolar cells as measured by chemiluminescence. The increase in chemiluminescence production in response to PI-3 virus was reduced in cells obtained from PI-3 virus pretreated animals (day 2, 42%; day 4, 65%; day 8, 22%; and day 16, 30%). In conclusion, PI-3 virus can stimulate broncho-alveolar cells and the virus-induced airway hyperresponsiveness is associated with an influx of inflammatory cells in the respiratory tract.
Folkerts
G
G
Department of Pharmacology, Faculty of Pharmacy, Utrecht University, Netherlands.
Van Esch
B
B
Janssen
M
M
Nijkamp
F P
FP
D000403:Airway Resistance; D000704:Analysis of Variance; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000473:pathology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D004804:Eosinophils; D006168:Guinea Pigs; D008163:Luminescent Measurements; D008214:Lymphocytes; D016676:Macrophages, Alveolar; D008297:Male; D009000:Monocytes; D009504:Neutrophils; D010224:Parainfluenza Virus 3, Human; D018184:Paramyxoviridae Infections / Q000473:pathology / Q000503:physiopathology*; D013047:Specific Pathogen-Free Organisms