Experimental rhinovirus infection increases human tissue kallikrein activation in allergic subjects.
BACKGROUND
Rhinovirus infection is a major cause of asthma exacerbations. While rhinovirus infection is known to generate kinins in the upper respiratory track, little is known about the effect of rhinovirus on kinin generation in the lower airway. We previously identified human tissue kallikrein (hTK) as the principal lung kininogenase during allergic airway inflammation. In this report we investigate the effect of experimental rhinovirus infection on hTK activity in the airways of atopic subjects with and without asthma.


METHODS
Eight atopic subjects, 4 with asthma, underwent bronchoscopy with lavage. At least 1 month later, subjects were inoculated with rhinovirus, then underwent repeat bronchoscopy with lavage 4 and 18 days later. hTK mRNA was measured in nasal scrape samples by quantitative real-time PCR. hTK activity (chromogenic substrate assay) and IL-8 levels (ELISA) were assessed in the bronchoalveolar lavage fluid.


RESULTS
At day 4 after rhinovirus inoculation, nasal hTK mRNA was modestly increased in both the rhinitis (1.7-fold) and asthmatic (2.1-fold) groups. A doubling or greater increase in hTK activity after rhinovirus infection was observed in all 4 asthmatic subjects (mean 19-fold increase) but only in 1 of 4 atopic subjects without asthma (mean 2-fold increase). Rhinovirus infection also increased the IL-8 protein level in bronchoalveolar lavage fluid, which correlated with hTK activity (R = 0.82).


CONCLUSIONS
Experimental rhinovirus infection in allergic asthmatic subjects is accompanied by increased lower airway hTK activation, which parallels the appearance of IL-8. Rhinovirus-induced hTK activation may contribute to airway inflammation and asthmatic exacerbations.
Christiansen
Sandra C
SC
Southern California Kaiser Permanente Medical Group, San Diego, Calif., USA.
Eddleston
Jane
J
Bengtson
Sara H
SH
Jenkins
Gavin R
GR
Sarnoff
Robert B
RB
Turner
Ronald B
RB
Gwaltney
Jack M
JM
Zuraw
Bruce L
BL
D000328:Adult; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000201:enzymology*; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D010850:Picornaviridae Infections / Q000201:enzymology* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D012229:Rhinovirus; D020840:Tissue Kallikreins / Q000235:genetics / Q000378:metabolism*
D016209:Interleukin-8; D012333:RNA, Messenger; D020840:Tissue Kallikreins