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Expression of ICAM-1 in Nasal Epithelium and Levels of Soluble ICAM-1 in Nasal Lavage Fluid During Human Experimental Rhinovirus Infection
Birgit Winther, MD;
Eurico Arruda, MD, PhD;
Theodore J. Witek, DrPH;
Steven D. Marlin, PhD;
Michael M. Tsianco, PhD;
Donald J. Innes, MD;
Frederick G. Hayden, MD
Arch Otolaryngol Head Neck Surg. 2002;128:131-136.
ABSTRACT
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Most rhinovirus serotypes use intercellular adhesion molecule-1 (ICAM-1)
as the receptor to enter cells, but ICAM-1 expression has not been detected
on normal nasal epithelial cells. During experimental rhinovirus infection,
expression of ICAM-1 on nasal epithelial cells was examined with immunohistochemical
staining of nasal scrape biopsy specimens, and levels of soluble ICAM-1 in
nasal lavage fluid were measured by sandwich enzyme-linked immunosorbent assay
technique. Expression of ICAM-1 on nasal epithelial cells increased following
inoculation in 20 of 23 infected subjects. The median number of ICAM-1–positive
cells per 6.25-mm2 area of stained biopsy specimen was 0 in control
samples (day 20 or 33 after inoculation), and in those without infection,
6 on day 1 (P .05), 14.5 on day 3 (P.01), 1.5 on day 5, and 0 on day 9. In a different group of volunteers,
soluble ICAM-1 in nasal lavage fluid was higher on days 1 and 3 compared with
preinoculation levels (P.001), but only 11 of
23 infected subjects had a 2-fold or greater increase. Up-regulation of ICAM-1
receptor expression on nasal epithelial cells occurred within 24 hours after
inoculation in experimental rhinovirus infections (prior to onset of symptoms)
and declined promptly by day 5.
INTRODUCTION
Most human rhinoviruses (HRVs) (the major receptor group) gain entrance
to nasal epithelial cells by a specific cellular receptor that has been identified
as intercellular adhesion molecule-1 (ICAM-1), a member of the immunoglobulin
superfamily.1-3
The natural ligand for the ß2 integrin leukocyte function-associated
antigen-1 (CD11a/CD18), which is widely expressed on leukocytes and various
other cells, ICAM-1 (CD54) can be up-regulated not only on endothelial cells
but also on epithelial cells in the airways. In vitro, a 12-fold increase
in ICAM-1 cell surface expression has been demonstrated in HRV-infected primary
bronchial epithelial cells.4 Expression of
ICAM-1 also occurs on cultured human nasal epithelial cells5
and on epithelial and endothelial cells of nasal biopsy specimens from subjects
during inflammatory states, such as allergic rhinitis.6-7
However, currently used methods have not detected ICAM-1 expression in noninflamed
nasal epithelium.5 An immunohistochemical study
of human adenoid epithelium has found that constitutive expression of ICAM-1
is not homogeneous but localized to the surface of a small number of cells.8
Shedding of an extracellular portion of ICAM-1, or soluble ICAM-1 (sICAM-1)
occurs as evidenced by its detection in certain body fluids. The level of
soluble ICAM-1 has been detected in sera of healthy individuals9
and is elevated in the peripheral blood of patients with bronchial asthma.10 The level of soluble ICAM-1 is also elevated in nasal
lavage fluid (NAL) from allergic patients during allergy season11
and has also been detected in NAL from patients with naturally acquired rhinovirus
colds.12
The role of ICAM-1 during rhinovirus infection may be complex. Increased
ICAM-1 expression may facilitate viral replication4;
ICAM-1 enriched HeLa-I cells support viral growth to a greater extent than
other cell types.13 Soluble ICAM-1 inhibits
HRV replication in cell culture,14-15
suggesting that endogenously produced sICAM-1 may exert an antiviral effect
and modify the course of HRV infection. Increases in polymorphonuclear leukocyte
concentrations in submucosal and nasal secretion are an integral part of the
inflammatory response to rhinovirus infection16;
blockade of cell-associated ICAM-1 by antibody has been shown to inhibit polymorphonuclear
leukocyte and eosinophil migration through endothelial cells in vitro.17-20 In
addition, sICAM-1 could interfere with normal intercellular interactions and
modify the immune response to HRV infection. In the present study, we examined
ICAM-1 expression on nasal epithelial cells and concentrations of sICAM-1
in NAL during experimental HRV infection.
SUBJECTS, MATERIALS, AND METHODS
VOLUNTEERS
Healthy young adults with serum-neutralizing antibody titer of 1:2 or
less to HRV serotypes 14 or 39 were recruited from the University of Virginia,
Charlottesville, community. All volunteers provided written informed consent
approved by the human investigation committee at the University of Virginia.
STUDY DESIGN
Levels of sICAM-1 were determined in 24 volunteers inoculated with HRV
39. Studies for ICAM-1 expression on nasal epithelial cells were conducted
in separate HRV studies with 33 adult volunteers as previously reported.21 Because samples were collected in separate studies,
contamination of NAL with serum ICAM-1 due to trauma from the biopsy was avoided.
VIRAL INOCULATION
Two different safety-tested virus pools were used: HRV 39 and HRV 14.
The rhinovirus pools were cell culture harvests of clinical isolates grown
in human embryonic lung fibroblast cultures22
and have been safety tested. Subjects were inoculated by nasal drops with
a volume of 100 µL per nostril repeated once for a total inoculum of
approximately 300 median tissue culture infective dose per subject. After
virus inoculation, the volunteers were isolated in hotel rooms and monitored
daily for illness on days 1 through 5.
NAL AND SECRETION COLLECTION
For measurement of sICAM-1, NAL samples were obtained before virus inoculation
and daily in the morning. Isotonic saline (5 mL per nostril) was instilled
in the nasal cavity with the patient's head hyperextended. After 5 to 10 seconds
the saline was expelled through the nose into a cup, with recovery of 6 to
8 mL. An aliquot (4 mL) was added to a 1-mL volume of concentrated (x5)
viral transport medium. This sample was also used for isolation of virus by
standard cell culture techniques.
For the nasal epithelial study, nasal secretions were blown onto plastic
sheets. Swabs of these secretions and throat swabs were collected 1 day before
inoculation with HRV and on each day thereafter and placed together in viral
transport medium for HRV isolation. This was done to avoid any possible effect
of the nasal-washing procedure on epithelial ICAM-1 expression.
sICAM-1 DETERMINATION
Aliquots of NAL were frozen and stored at -70°C for up to
3 months and underwent 1 to 2 freeze-thaw cycles prior to sICAM-1 analysis.
Soluble ICAM-1 was measured by a sandwich enzyme-linked immunosorbent assay
technique (Bender Med Systems, Vienna, Va). The lower detection level was
3 ng/mL of NAL. Assays were done under masked conditions without knowledge
of infection and illness status of the volunteers.
NASAL SCRAPE BIOPSIES
Four nasal scrape biopsies were performed with a plastic curette from
each individual from the anterior part of the inferior turbinate on days 1,
3, and 5. The fourth biopsy was performed on days 9, 20, or 33 after inoculation.
Biopsy specimens were immediately fixed in buffered 4% paraformaldehyde, included
in a human plasma clot, and embedded in paraffin for sectioning.21
IMMUNOHISTOCHEMICAL STUDIES
Tissue sections mounted on poly-L-lysine–coated slides were deparaffinized,
treated with methanol peroxide to block endogenous peroxidase for 10 minutes,
and then immersed in 10mM citrate buffer (pH 6.0) and boiled in the microwave
oven for 30 minutes on the highest setting, replenishing the volume with distilled
water every 5 minutes. The slides were allowed to cool for 10 to 15 minutes
before being loaded onto the automated immunostainer (Ventana Enhanced System,
Ventana Medical Systems, Tucson, Ariz). The diaminobenzidine immunohistochemistry
procedure was done according to the instructions for the operation of the
machine. Slides were incubated for 32 minutes with the primary monoclonal
antibody anti-CD54 (Dako, Carpinteria, Calif) at a 1:20 dilution and then
sequentially incubated with the following reagents of the diaminobenzidine
detection system: endogenous biotin blocker, secondary biotinylated antibody,
avidin-horseradish peroxidase, and diaminobenzidine complex, and a copper-enhancing
solution for improved visualization of the diaminobenzidine reaction product.
All washes between steps were done with the wash buffer provided by the manufacturer.
Sections were counterstained with Harris hematoxylin. Expression of ICAM-1
on vascular endothelial cells in sections of human adenoid was used as a positive
control. A section from each biopsy specimen was stained in parallel with
the negative control irrelevant antibody provided by the instrument's manufacturer.
One section from each of the 4 nasal epithelial biopsy specimens from
33 subjects (132 sections) was analyzed by light microscopy under blinded
conditions. The number of ICAM-1 expressing cells was counted in an area of
6.25 mm2 using an eyepiece with a cell-counting grid. Only areas
with a continuous sheet of epithelium that covered the entire area of the
grid (6.25 mm2) were included in the analysis.
VIRUS CULTURES AND SEROLOGY
Nasal lavage fluid was inoculated onto monolayers of human embryonic
lung fibroblast cells (MRC-5 and/or WI-38 strain) in screw-capped tubes for
rhinovirus detection.23 Isolates recovered
were confirmed by immunologic methods (neutralization assay); paired serum
samples collected before and 3 weeks after virus inoculation were used for
measuring neutralizing antibodies to HRV.
INFECTION AND ILLNESS
A volunteer was considered infected if he/she shed the virus and/or
had a 4-fold or greater rise in serum neutralizing antibody titer. A volunteer
was considered to have illness if he/she had a minimum symptom score of 6,
based on a modification of the Jackson respiratory illness scoring system.24 Sham-inoculated volunteers who developed cold symptoms
had nasal secretions tested for HRV by reverse transcriptase–polymerase
chain reaction25 and excluded from analysis
if found positive.
STATISTICS
Statistical analyses of sICAM-1 levels in NAL were performed using SAS
6.12 (SAS Institute Inc, Cary, NC). Soluble ICAM-l levels were modeled separately
for the HRV-positive group using repeated-measures analysis of variance. The
underlying assumptions and the impact of data transformation and outliers
were investigated in sensitivity analyses. Analyses of sICAM-1 level to the -2
power are reported here because these residuals were the only ones that satisfied
the normality assumptions. However, all repeated-measures analyses and, in
addition, simple Wilcoxon signed rank tests of differences from day 0 led
to the same qualitative results. The association between increases in sICAM-1
levels before and after inoculation and other measures (Jackson cold status,
viral shedding, and seroconversion) was assessed by dichotomizing change in
sICAM-1 level (below and above a 2-fold increase) and applying a Fisher exact
test. The association between 2-fold increases in sICAM-1 level and the median
total mucus weight was tested using a Wilcoxon rank sum test. Cellular expression
of ICAM-1 in nasal biopsy specimens of a different group of HRV-infected subjects
compared with noninfected sham-inoculated subjects was analyzed by the Mann-Whitney
test. Statistical significance was indicated for P
values of .05 or below without adjustment for multiple comparisons.
RESULTS
INFECTION AND ILLNESS
In the study of sICAM-1 elaboration, 21 (88%) of 24 volunteers became
infected, 2 were not infected, and 1 had a wild rhinovirus detecg on the first
study day. This volunteer was excluded from the analysis. Of the HRV-infected
volunteers, 20 (95%) of 21 had colds by standard criteria. To evaluate ICAM-1
on epithelial cells, 23 (88%) of 26 HRV-inoculated subjects developed infection
and 18 (78%) of 23 infected developed clinical colds. One sham-inoculated
volunteer who was symptomatic and found positive for HRV by reverse transcriptase–polymerase
chain reaction was excluded.
NAL sICAM-1
Levels of sICAM-1 appeared to increase following virus inoculation in
the HRV-infected subjects (Figure 1).
These increases were significant on day 1 (P<.001)
and day 3 (P<.001) after inoculation compared
with preinoculation (day 0) levels in the HRV group, while the increase at
day 5 did not quite achieve significance (P = .06).
Overall, 11 (52%) of 21 HRV-infected subjects showed a 2-fold or greater increase
in NAL sICAM levels during the 5 days following HRV inoculation. There was
no detectable association between a 2-fold increase in sICAM level in NAL
and symptomatic colds by the Jackson criteria, mucus weight, viral shedding,
or seroconversion.
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Figure 1. Soluble intercellular adhesion
molecule-1 (ICAM-1) levels in nasal lavage fluid by study day. Increase at
postinoculation day 3 vs preinoculation day 0 is significant for the human
rhinovirus (HRV) group (P = .01). Solid lines denote
means. Data are shown on logarithmic scale to facilitate visualizing extreme
values, but analysis was performed on raw data using analysis of variance
with terms for patient and day. Number of subjects depicted are 21 and 2 for
the HRV-positive and HRV-negative groups, respectively.
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ICAM-1 EXPRESSION ON NASAL EPITHELIUM
Nasal epithelial cell expression of ICAM-1 (Figure 2) varied in relation to time of the infection (Table 1). Twenty of 23 HRV-infected volunteers
had an increase in number of ICAM-1–positive nasal epithelial cells.
The increase in ICAM-1 expression had already occurred on days 1 and 3 following
inoculation, and the numbers of ICAM-1–expressing cells decreased by
day 5. From the same volunteers, the control biopsy specimens obtained on
day 20 or 33 were uniformly negative except for 1 (subject 11, Table 1). Unfortunately, no viral cultures were collected at this
time. Only 3 volunteers (subjects 1, 4, and 7) did not have an increase above
the range of the control biopsy specimens. The median numbers of cells expressing
ICAM-1 per 6.25-mm2 area of biopsy material obtained on days 1
and 3 were significantly increased (day 1, P.05;
day 3, P.01) in subjects infected with HRV compared
with the noninfected sham-inoculated subjects. No significant differences
in the number of ICAM-1–positive cells were found between subjects with
cold symptoms and those without colds. Few cells expressing ICAM-1 (median,
0; range, 0-8 per 6.25-mm2 area) were detected in the nasal biopsy
specimens from 5 of the 6 sham-inoculated subjects. One sham-inoculated subject
who did not develop infection or cold symptoms had a higher number of ICAM-1–positive
cells (22 per 6.25-mm2 area) on day 1 (Table 1). Unfortunately, material from that subject was insufficient
for analysis on days 3 and 5. On day 33 after infection, the nasal biopsy
specimen from that subject still showed a high number of ICAM-1–positive
cells (8 per 6.25-mm2 area), suggesting a higher expression of
ICAM-1, either constitutive or secondary to subclinical inflammation.
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Figure 2. Nasal scrape biopsy specimen from
the inferior turbinate on day 3 from a patient with rhinovirus infection.
Immunohistochemical staining with anti-CD54 shows positive staining of the
surface membrane of an epithelial cell.
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Expression of ICAM-1 on Nasal Epithelial Cells in Scrape Biopsy Specimens
From Rhinovirus-Infected and Sham-Inoculated Volunteers*
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COMMENT
This study demonstrates that ICAM-1 expression on nasal epithelial cells
was up-regulated within 24 hours following HRV inoculation as determined by
immunohistochemical staining and decreased rapidly to baseline by day 9. This
was mirrored by an increase in sICAM-1 levels in NAL, although the changes
were modest and only significantly different on day 3 following HRV inoculation.
Previous information on ICAM-1 in the upper airway mucosa during HRV infection
is sparse. Hildebrandt and coworkers12 found
an increase in sICAM-1 levels in NAL during the acute phase of naturally acquired
colds compared with convalescence. The magnitude of change observed in that
study over time was comparable with the increase observed in the present study.
It is of interest that the increase in sICAM-1 levels in our study did not
correlate with occurrence of illness, nasal mucus weight, virus shedding,
or seroconversion, and that it occurred prior to the full development of peak
symptoms.
Expression of ICAM-1 in the airway mucosa is very low in the noninflamed
nose,6 nasopharynx,8
and bronchial mucosa26-29
under basal conditions. However, during inflammation ICAM-1 expression can
be up-regulated not only on the endothelial cells but also on epithelial cells
in the airway mucosa.5, 30-33
The present study also found low-level expression of ICAM-1 on nasal epithelial
cells under baseline conditions but increased expression during the early
phase of HRV infection. Expression of ICAM-1 in airway epithelium and endothelial
cells in mice is up-regulated in response to various stimuli including ozone
exposure,34 interleukin 5,35
tumor necrosis factor  , interleukin 1,36
and activated CD8+ T cells.37 Christensen
et al38 demonstrated a correlation between
elevated circulating ICAM-1 levels in serum and virus-induced T-cell activation
during lymphocytic choriomeningitis virus infection, which suggested release
of ICAM-1 into the bloodstream. It is not clear if the source of sICAM-1 detection
in NAL following HRV infection is from up-regulated ICAM-1 expression on nasal
epithelial cells or serum transudation. In asthmatic subjects sICAM-1 levels
in bronchoalveolar lavage fluid following experimental antigen stimulation
were higher than what could be explained by serum transudation. The bronchoalveolar
lavage to serum ratio of sICAM-1 was 250 times higher than the ratio of albumin,
which suggested that sICAM was derived from additional sources in the lower
respiratory tract.39 Our demonstration of increased
ICAM-1 expression on nasal epithelial cells also points to the mucosa as the
likely source of sICAM-1 in nasal secretions.
The biological significance of increased ICAM-1 expression on nasal
epithelial cells and sICAM-1 shedding in NAL fluid is not fully understood.
Increased cell surface ICAM-1 expression could result in increased viral replication,
whereas increased sICAM-1 in NAL conceivably may inhibit HRV receptor–binding
in vivo, analogous to HRV inhibition by recombinant sICAM-1 in vitro. Exogenous
application of sICAM-1 has been shown to reduce viral replication and illness
following experimental HRV infection.40 We
did not find any clear relationship between the surface expression of ICAM-1
and expression of clinical colds of experimental HRV infection. However, the
strength of this conclusion is limited by our relatively small sample size.
Cell surface expression of ICAM-1 may have a central role in recruitment
of polymorphonuclear leukocyte traffic from the vascular bed through the airway
epithelium and into nasal mucus. In the lower airways, ICAM-1 has been demonstrated
on the alveolar surface in areas undergoing alveolar repair, suggesting that
ICAM-1 may participate in controlling the movement of leukocytes onto and
over the alveolar surface.41 Further studies
are needed to evaluate how ICAM-1 expression relates to viral replication
and the cytokine response in the upper airway tract mucosa to determine if
up-regulation of HRV's "own" human cell surface receptor (ICAM) fosters virus
replication in a feedback mechanism.
AUTHOR INFORMATION
Accepted for publication September 19, 2001.
Corresponding author and reprints: Frederick G. Hayden, MD, University
of Virginia Health System, Department of Internal Medicine, Box 800473, Charlottesville,
VA 22908 (e-mail: fgh{at}virginia.edu).
From the Departments of Otolaryngology and Pediatrics (Dr Winther),
Internal Medicine (Drs Arruda and Hayden), and Pathology (Drs Arruda, Innes,
and Hayden), University of Virginia School of Medicine, Charlottesville; and
Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Conn (Drs Witek, Marlin,
and Tsianco). Dr Arruda is now with the University of Sào Paulo School
of Medicine, Department of Parasitology, Microbiology and Immunology, Ribeirao
Preto, São Paulo, Brazil.
REFERENCES
| |
1. Rossmann MG, Palmenberg AC. Conservation of the putative receptor attachment site in picornaviruses. Virology. 1988;164:373-382.
FULL TEXT
|
ISI
| PUBMED
2. Staunton DE, Merluzzi VJ, Rothlein R, Barton R, Marlin SD, Springer TA. A cell adhesion molecule, ICAM-1 is the major surface receptor for
rhinoviruses. Cell. 1989;56:849-853.
FULL TEXT
|
ISI
| PUBMED
3. Greve JM, Davis G, Meyer AM, et al. The major human rhinovirus receptor is ICAM-1. Cell. 1989;56:839-847.
FULL TEXT
|
ISI
| PUBMED
4. Papi A, Johnston SL. Rhinovirus infection induces expression of its own receptor intercellular
adhesion molecule 1 (ICAM-1) via increased NF- B–mediated transcription. J Biol Chem. 1999;274:9707-9720.
FREE FULL TEXT
5. Altman LC, Ayars GH, Baker C, Luchtel DL. Cytokines and eosinophil-derived cationic proteins upregulate intercellular
adhesion molecule-1 on human nasal epithelial cells. J Allergy Clin Immunol. 1993;92:527-536.
FULL TEXT
|
ISI
| PUBMED
6. Ciprandi G, Pronzato C, Ricca V, Passalacqua G, Bagnasco M, Caronica GW. Allergen-specific challenge induces intercellular adhesion molecule
1 (ICAM-1 or CD54) on nasal epithelial cells in allergic subjects. Am J Respir Crit Care Med. 1994;150:1653-1659.
ABSTRACT
7. Lee BJ, Naclerio RM, Bochner BS, Taylor RM, Lim MC, Baroody FM. Nasal challenge with allergen upregulates the local expression of vascular
endothelial adhesion molecules. J Allergy Clin Immunol. 1994;94:1006-1016.
FULL TEXT
|
ISI
| PUBMED
8. Winther B, Greve JM, Gwaltney JM Jr, et al. Surface expression of intercellular adhesion molecule 1 on epithelial
cells in the human adenoid. J Infect Dis. 1997;176:523-525.
ISI
| PUBMED
9. Rothlein R, Mainolfi EA, Czajkowski M, Marlin SD. A form of circulating ICAM-1 in human serum. J Immunol. 1991;147:3788-3793.
ABSTRACT
10. Hashimoto S, Imai K, Kobayashi T, et al. Elevated levels of soluble ICAM-1 in sera from patients with bronchial
asthma. Allergy. 1993;48:370-372.
ISI
| PUBMED
11. Kato M, Hattori T, Kitamura M, Beppu R, Yanagita N, Nakashima I. Soluble ICAM-1 as a regulator of nasal allergic reaction under natural
allergen provocation. Clin Exp Allergy. 1995;25:744-748.
FULL TEXT
|
ISI
| PUBMED
12. Hildebrandt MH, Hopken KL, Rosseler ST, Bachert C. Increased levels of proinflammatory cytokines and soluble intercellular
adhesion molecule (sICAM) in nasal secretions of patients during naturally
acquired rhinovirus infection [abstract]. Allergologie. 1996;1:43.
13. Arruda E, Crump CE, Rollins BS, Ohlin A, Hayden FG. Comparative susceptibility of human fibroblasts and HeLa cells for
isolation of human rhinovirus. J Clin Microbiol. 1996;34:1277-1279.
ABSTRACT
14. Arruda E, Crump CE, Marlin SD, Merluzzi VJ, Hayden FG. In vitro studies of the antirhinovirus activity of soluble intercellular
adhesion molecule-1. Antimicrob Agents Chemother. 1992;36:1186-1191.
FREE FULL TEXT
15. Crump CE, Arruda E, Hayden FG. In vitro inhibitory activity of soluble ICAM-1 for the numbered serotypes
of human rhinovirus. Antivir Chem Chemother. 1993;4:323-337.
16. Winther B. The effect on the nasal mucosa of respiratory viruses (common cold). Dan Med Bull. 1994;41:193-204.
ISI
| PUBMED
17. Tosi MF, Stark JM, Smith CW, Hamedani A, Gruenert DC, Infeld MD. Induction of ICAM-1 expression on human airway epithelial cells by
inflammatory cytokines: effects on neutrophil-epithelial cells adhesion. Am J Respir Cell Mol Biol. 1992;7:214-221.
18. Molina E, Nakajima N, Jiang Z, Chonmaitree T, Patel JA. Role of IL-8 and ICAM-1 in polymorphonuclear leukocyte (PMN) migration
through respiratory syncytial virus (RSV)–infected pulmonary epithelial
cells [abstract]. J Investig Med. 1996;44:72A.
19. Tang WW, Yi ES, Remick DG, et al. Intratracheal injection of endotoxin and cytokines, IX: contribution
of CD 11a/ICAM-1 to neutrophil emigration. Am J Physiol. 1995;269:L653-L659.
20. Smith CW, Marlin SD, Rothlein R, Toman C, Anderson DC. Cooperative interaction of LFA-1 and Mac1 with intercellular adhesion
molecule-1 in facilitating adherence and transendothelial migration of human
neutrophils in vitro. J Clin Invest. 1989;83:2008-2017.
21. Arruda E, Boyle TR, Winther B, Pevear DC, Gwaltney JM Jr, Hayden FG. Localization of human rhinovirus replication in the upper respiratory
tract by in situ hybridization. J Infect Dis. 1995;171:1329-1333.
ISI
| PUBMED
22. Gwaltney JM Jr, Hendley JO, Hayden FG, et al. Updated recommendations for safety-testing of viral inocula used in
volunteer experiments on rhinovirus colds. Prog Med Virol. 1992;39:256-263.
ISI
| PUBMED
23. Hamparian W. Rhinovirus. In: Lennette EH, Schmidt NJ, eds. Viral, Rickettsial
and Chlamydial Infections. 5th ed. Washington, DC: American Public
Health Association; 1979:535-575.
24. Jackson GG. Transmission of the common cold to volunteers under controlled conditions,
I: the common cold as a clinical entity. Arch Intern Med. 1958;101:267-278.
FULL TEXT
25. Pitkäranta A, Jero J, Arruda E, Virolainen A, Hayden FG. Polymerase chain reaction-based detection of rhinovirus, respiratory
syncytial virus, and coronavirus in otitis media with effusion. J Pediatr. 1998;133:390-394.
FULL TEXT
|
ISI
| PUBMED
26. Bentley AM, Durham SR, Robinson DS, et al. Expression of endothelial and leukocyte adhesion molecules intercellular
adhesion molecule-1, E selectin, and vascular cell adhesion molecule-1 in
the bronchial mucosa in steady-state and allergen-induced asthma. J Allergy Clin Immunol. 1993;92:857-868.
FULL TEXT
|
ISI
| PUBMED
27. Vignola AM, Campbell AM, Chanez P, et al. HLA-DR and ICAM-1 expression on bronchial epithelial cells in asthma
and chronic bronchitis. Am Rev Respir Dis. 1993;148:689-694.
ISI
| PUBMED
28. Stefano AD, Maestrelli P, Roggeri A, et al. Upregulation of adhesion molecules in the bronchial mucosa of subjects
with chronic obstructive bronchitis. Am J Respir Crit Care Med. 1994;149:803-810.
ABSTRACT
29. Gosset P, Tillie-Leblond I, Janin A, et al. Expression of E-selectin, ICAM-1 and VCAM-1 on bronchial biopsies from
allergic and non-allergic asthmatic patients. Int Arch Allergy Immunol. 1995;106:69-77.
ISI
| PUBMED
30. Subauste MC, Jacoby DB, Richards SM, Proud D. Infection of a human respiratory epithelial cell line with rhinovirus:
induction of cytokine release and modulation of susceptibility to infection
by cytokine exposure. J Clin Invest. 1995;96:549-557.
31. Canonica GW, Ciprandi G, Pesce GP, Buscaglia S, Paolieri F, Bagnasco M. ICAM-1 on epithelial cells in allergic subjects: a hallmark of allergic
inflammation. Int Arch Allergy Immunol. 1995;107:99-102.
ISI
| PUBMED
32. Patel JA, Kunimoto M, Sim TC, et al. Interleukin mediates the enhanced expression of intercellular
adhesion molecule-1 in pulmonary epithelial cells infected with respiratory
syncytial virus. Am J Respir Cell Mol Biol. 1995;13:602-609.
ABSTRACT
33. Arnold R, Werchau H, Konig W. Expression of adhesion molecules (ICAM-1) on human epithelial cells
(A549) after respiratory syncytial virus infection. Int Arch Allergy Immunol. 1995;107:392-393.
ISI
| PUBMED
34. Takahashi N, Yu XY, Schofield BH, et al. Expression of ICAM-1 in airway epithelium after acute ozone exposure
in the mouse. J Appl Physiol. 1995;79:1753-1761.
FREE FULL TEXT
35. Terada N, Konno A, Fukuda S, et al. Interleukin-5 upregulates intercellular adhesion molecule-1 gene expression
in the nasal mucosa in nasal allergy but not in nonallergic rhinitis. Int Arch Allergy Immunol. 1995;106:139-145.
ISI
| PUBMED
36. Tosi MF, Stark JM, Smith CW, Hamedani A, Gruenert DC, Infeld MD. Induction of ICAM-1 expression on human airway epithelial cells by
inflammatory cytokines: effects on neutrophil-epithelial cell adhesion. Am J Respir Cell Mol Biol. 1992;7:214-221.
37. Marker O, Scheynius A, Christensen JP, Thomsen AR. Virus-activated T cells regulate expression of adhesion molecules on
endothelial cells in sites of infection. J Neuroimmunol. 1995;62:35-42.
FULL TEXT
|
ISI
| PUBMED
38. Christensen JP, Johansen J, Marker O, Thomsen AR. Circulating intercellular adhesion molecule-1 (ICAM-1) as an early
and sensitive marker for virus-induced T cell activation. Clin Exp Immunol. 1995;102:268-273.
ISI
| PUBMED
39. Takahashi N, Liu MC, Proud D, Yu XY, Hasegawa S, Spannhake EW. Soluble intracellular adhesion molecule 1 in bronchoalveolar lavage
fluid of allergic subjects following segmental antigen challenge. Am J Respir Crit Care Med. 1994;150:704-709.
ABSTRACT
40. Turner RB, Wecker MT, Pohl G, et al. Efficacy of tremacamra, a soluble intercellular adhesion molecule 1,
for experimental rhinovirus infection: a randomized clinical trial. JAMA. 1999;281:1797-804.
FREE FULL TEXT
41. Gonzalez S, Hards J, van Eeden S, Hogg JC. Expression of adhesion molecules in cigarette smoke induce airway obstruction. Eur Respir J. 1996;9:1995-2001.
ABSTRACT
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Human Rhinovirus Selectively Modulates Membranous and Soluble Forms of Its Intercellular Adhesion Molecule-1 (ICAM-1) Receptor to Promote Epithelial Cell Infectivity
Whiteman et al.
J. Biol. Chem. 2003;278:11954-11961.
ABSTRACT
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