1. J_ID: LARY Customer A_ID: 08-0176.R1 Date: 2-February-09 Stage: Page: 1
The Laryngoscope
V 2009 The American Laryngological,
C
Rhinological and Otological Society, Inc.
Anti-Intercellular Adhesion Molecule-1
Antibody’s Effect on Noise Damage
Michael D. Seidman, MD, FACS; Wenxue Tang, MD; Najeeb Shirwany, MD; Uma Bai, PhD;
Cory J. Rubin, MD; Joseph P. Henig, MS; Wayne S. Quirk, PhD
Objectives/Hypothesis: The purpose of this mean auditory threshold shifts at all five test fre-
study was to investigate possible preventive effects of quencies (P < .05) when compared to control.
anti-intercellular adhesion molecule-1 antibody (anti- Conclusions: Blocking the cascade of reactive
ICAM-1 Ab) on noise-induced cochlear damage as oxygen species (ROS) generation by using anti-ICAM-
assessed by changes in auditory thresholds and coch- Ab protects against noise-induced hearing loss.
lear blood flow. Key Words: ICAM-1, noise-induced hearing loss,
Study Design: A controlled animal study. Pre- temporary threshold shifts, rat.
treated rats with anti-ICAM-1 Ab or saline control, fol- Laryngoscope, 000:000–000, 2009
lowed with exposure to 72 continuous hours of broad
band noise (107 dB SPL), and 24 hours after noise ex-
posure treated again with anti-ICAM-1 Ab or saline.
Methods: Eighteen healthy male Fischer rats INTRODUCTION
(200–250 g) were used. Sixteen were randomly Intense noise exposure initiates a cascade of events,
selected to study noise-induced temporary threshold which ultimately results in cell death and cochlear dam-
shifts. The remaining two rats were used to study age. A significant body of evidence has revealed that
cochlear blood flow (CBF), using laser Doppler flow- noise exposure produces profound cochlear microcircula-
metry and blood pressure measurements. tory changes, including hypoperfusion and ischemia.
Results: Rats treated with anti-ICAM-1 Ab Studies using intravital microscopy, Laser Doppler flow-
(1.875 mg/kg, intravenously) showed attenuated tem-
metry, and microcast techniques have demonstrated
porary threshold shifts (TTS) compared to controls.
Both groups showed a partial threshold recovery 72 reduced cochlear blood flow, decreased red blood cell ve-
hours following noise exposure, normal for this noise locity, capillary constriction, and increased vascular
exposure paradigm. Comparisons of baseline and permeability during noise exposure.1–3 The oxidative
post-treatment measurements of CBF and mean arte- stress that results from hypoxia and ischemia produces
rial blood pressure revealed no significant changes. a variety of damaging reactive oxygen species (ROS),
Anti-ICAM-1 Ab animals displayed significantly lower which includes hydrogen peroxide, the superoxide anion,
and the hydroxyl radical.4,5 The accumulation of ROS,
From the Department of Otolaryngology (W.T.), Emory University cytokines, and chemokines that are associated with hy-
School of Medicine, Atlanta, Georgia, U.S.A., Department of
Otolaryngology (M.D.S., U.B., C.J.R.), Henry Ford Health System, Detroit, poxia and ischemia promotes the expression of
Michigan, U.S.A., Department of Physiology (N.S.), Oklahoma University intercellular adhesion molecule-1 (ICAM-1) in endothe-
Health Sciences Center, Oklahoma City, Oklahoma, U.S.A., Burnham lial cells, which subsequently leads to neutrophil-
Institute for Medical Research (J.P.H.), La Jolla, California, U.S.A., and
Department of Psychology (W.S.Q.), Central Washington University, endothelial cell adhesion.6 This process results in
Ellensburg, Washington, U.S.A. increased circulating tissue levels of various cytokines,
Editor’s Note: This Manuscript was accepted for publication leukotrienes, thromboxanes, platelet activating factor,
November 11, 2008.
complement components, elastases, and other enzymes,
This research was performed at Henry Ford Health System,
Department of Otolaryngology, under the supervision of Dr. Michael D. as well as additional formation of ROS. Typically, the
Seidman. effects of these molecules and their activation are delete-
This research was presented as a poster presentation at the Asso- rious to the cells and tissues involved. Some of these
ciation for Research in Otolaryngology Mid-Winter Meeting, St. Peters-
burg, Florida, U.S.A. on February 4, 2001. Funding was supported in substances up regulate leukocyte adhesion receptors,
part by the following NIH grants: NIDCD-DC00101-05 (MDS), increase vascular permeability, damage tissues directly,
1R21AT001067-01-03, NCCAM, July 2003–2005. Pharmacia & Upjohn and impair endothelial function, which leads to edema,
Company donated the anti-ICAM-1 antibody.
Send correspondence to Wenxue Tang, MD, Henry Ford Health
vascular insufficiency, and ultimately necrosis.7
System, Department of Otolaryngology – Head & Neck Surgery, Division Previous studies have demonstrated that anti-
of Otology and Neurotology, 6777 West Maple Road, West Bloomfield, MI oxidants and scavengers of ROS attenuate ischemia/
48323. E-mail: mseidma1@hfhs.org
reperfusion-induced and noise-induced cochlear dam-
DOI: 10.1002/lary.20109 age.4,8 Furthermore, anti-ICAM-1 Ab has been shown to
Laryngoscope 000: Month 2009 Seidman et al.: Anti-ICAM-1 Ab and Noise Damage
1
ID: kumarpr I Black Lining: [ON] I Time: 19:21 I Path: //xinchnasjn/01Journals/Wiley/3b2/LARY/Vol00000/080117/APPFile/C2LARY080117

2. J_ID: LARY Customer A_ID: 08-0176.R1 Date: 2-February-09 Stage: Page: 2
attenuate damage in brain, heart, kidney, and other tissues zoo, MI) over a 2-minute interval, while control group animals
where ICAM-1 plays a critical role in ischemia-induced (n ¼ 8) were infused in the same manner with an equivalent
damage.9 Prior studies have shown that ICAM-1 also plays volume of the vehicle control (saline). Animals were then imme-
an important role not only in middle ear diseases, including diately placed in an acoustically-insulated noise booth
(Industrial Acoustics, New York, NY) and exposed to 107 dB
otitis media10 and cholesteatoma,11 but also in inner ear
SPL broadband noise for 72 continuous hours. Twenty-four
inflammation12 and carcinoma of the head and neck.13 The hours after the onset of the noise exposure, the treatment group
purpose of our study was to assess the possible protective animals received an additional half-dose of anti-ICAM-1 Ab
effect of anti-ICAM-1 Ab on noise-induced cochlear damage (0.625 mg/kg), while the control group animals received an
by evaluating noise-induced TTS. equivalent volume of saline. Caging was designed to be acousti-
cally transparent, and calibration measurements throughout
the cage revealed a variance of 0.4–0.8 dB from the front of the
MATERIAL AND METHODS
cage to the back. To determine TTS, ABR measurements were
Subjects recorded 10 minutes after the completion of the noise exposure.
A total of 18 healthy male Fischer rats (200–250 g) were Final ABR measurements were recorded 72 hours after the
used in this study. Sixteen animals were used to study noise- noise exposure.
induced TTS as determined by auditory brainstem response
(ABR) measurements. These animals were randomly assigned
to either the anti-ICAM-1 Ab treatment group (n ¼ 8) or the
control group (n ¼ 8). The remaining two rats were used to
study Cochlear blood flow (CBF) using laser Doppler flowmetry
CBF
and blood pressure measurements. The use of experimental ani- CBF experiments were conducted on two healthy male Fi-
mals for this study was approved by the Care for Experimental scher rats. The animals were anesthetized as previously
Animals Committee at Henry Ford Health System. Additionally, described. A small opening was made in the right bulla and a
all procedures were conducted in strict compliance with the 24-gauge laser Doppler needle probe was positioned over the ba-
National Institutes of Health guidelines for experimental ani- sal turn of the cochlea. A small amount of petroleum jelly was
mal subjects. applied to the tip of the laser probe to enhance optical coupling
of the laser signal to the otic capsule. The hole in the bulla was
then covered with bone wax. A laser Doppler flow meter (BLF
ABR 21D; Transonic Systems Inc., Ithaca, NY) was used to record
Baseline ABR measurements were obtained from 16 CBF measurements (represented as tissue perfusion units or
healthy male Fischer rats. Animals were anesthetized with a TPU). Mean arterial blood pressure (BP) was monitored by a
mixture of ketamine and xylazine (100 mg/kg and 15 mg/kg, blood pressure transducer connected to a catheter that was
respectively), given subcutaneously. Auditory stimuli were gen- inserted into the left femoral artery. Baseline CBF and BP
erated using a D/A converter (Model DA3-2; Tucker-Davis measurements were recorded at 1-minute intervals for 33
Technologies (TDT), Gainesville, FL) with a sampling frequency minutes. anti-ICAM-1 Ab (1.25 mg/kg) was then intravenously
of 100 kHz. The output of the D/A converter was connected to a administered. CBF and BP measurements were continued for
programmable attenuator (Model PA4; TDT), a weighted an additional 75 minutes.
summer (Model SM3; TDT), a headphone buffer (Model HB6;
TDT), and an earphone (Model DT-48; Beyer Dynamic, Heil-
bronn, Germany), which was placed in close approximation to
the tympanic membrane of the animal. The stimuli consisted of RESULTS
tone bursts with a rise/fall time of 1 ms, a duration of 15 ms,
and a period of 100 ms. A series of stimuli were produced at 3, ABR
6, 9, 12, and 18 kHz test frequencies with intensities ranging ABR measurements were recorded at five test fre-
from 5–100 dB SPL in 5 dB increments. The system was cali- quencies (3, 6, 9, 12, and 18 kHz) as previously
brated at the tympanic membrane using a probe microphone described.14 Baseline ABR measurements obtained prior
(Model ER-7C; Etymotic Research, Elk Grove Village, IL), to anti-ICAM-1 Ab treatment and noise exposure indi-
which was connected to an A/D converter (Model AD2, TDT) cated that there were no significant differences in mean
and a computer. Automated calibrating routines were used for
auditory thresholds between the treatment and control
online calibration?
ABRs were collected using subcutaneous electrodes (Model
groups (Fig. 1). Ten minutes following exposure to F1
E2; Grass Instruments, Quincy, MA) and placed at the vertex and 72 hours of continuous 107 dB SPL broadband noise,
under both pinnae of each animal. This output was channeled anti-ICAM-Ab (1.25 mg/kg) treatment group animals dis-
into a biologic amplifier (Model P5 Series; Grass Instruments) played significantly lower mean auditory threshold
with a gain of Â100,000. The response was filtered between 0.3 shifts at all five test frequencies (3 kHz (P ¼ .02), 6 kHz
and 3.0 kHz, and then the output was sent to an A/D converter (P ¼ .047), 9 kHz (P ¼ .042), 12 kHz (P ¼ .0095) and
(Model AD2; TDT). Custom-designed software allowed these 18 kHz (P ¼ .0098)) when compared to control (Fig. 2). F2
responses to be displayed with a sampling rate of 50 kHz in real Seventy-two hours following noise exposure, a reduction
time on a computer monitor. For each recording, a 20-ms neural
in mean auditory threshold shifts was observed in both
response was averaged 1,024 times. For each of the five test fre-
the treatment and control groups (Fig. 3), indicating a F3
quencies, auditory thresholds were determined by identifying the
smallest intensity (in dB SPL) at which ABR wave forms became partial recovery of auditory sensitivity. Intergroup com-
evident. parison showed little or no significant differences in
Following baseline ABR testing, treatment group animals auditory threshold shifts between treatment and control.
(n ¼ 8) were intravenously infused with 1.25 mg/kg of anti- This type of recovery is characteristic of the noise expo-
ICAM-1 Ab (Gift of Discovery Research, Upjohn Co., Kalama- sure paradigm, which primarily produces TTS.
Laryngoscope 000: Month 2009 Seidman et al.: Anti-ICAM-1 Ab and Noise Damage
2
ID: kumarpr I Black Lining: [ON] I Time: 19:21 I Path: //xinchnasjn/01Journals/Wiley/3b2/LARY/Vol00000/080117/APPFile/C2LARY080117

3. J_ID: LARY Customer A_ID: 08-0176.R1 Date: 2-February-09 Stage: Page: 3
Fig. 1. Baseline auditory brainstem response thresholds. Mean au- Fig. 2. Auditory threshold shifts (post-noise: 10 min.). Mean audi-
ditory threshold levels of treatment group rats (dashed line) and tory threshold shifts of anti-intercellular adhesion molecule-1 anti-
control group rats (solid line) at five test frequencies (3, 6, 9, 12, body (anti-ICAM-1 Ab) (1.25 mg/kg) treatment group rats (dashed
and 18 kHz). Measurements were obtained prior to treatment with line) exposed to 72 hours of continuous 107 dB sound pressure
anti-intercellular adhesion molecule-1 antibody (anti-ICAM-1 Ab) level (SPL) broad band noise and control (solid line). Measure-
and noise exposure. SPL ¼ sound pressure level. ments were obtained 10 minutes following noise exposure at five
test frequencies (3, 6, 9, 12, and 18 kHz).
CBF that: 1) ischemia in vivo followed by reperfusion in iso-
CBF and BP measurements were obtained as pre- lated perfuse kidneys resulted in neutrophil retention; 2)
F4 viously described. Figure 4 depicts CBF shifts (repre- retained neutrophils adversely affect renal function; and
sented as a percentage change from mean baseline CBF)
F5 and Figure 5 depicts a BP recording from a representa-
tive animal taken over a period of 108 minutes. No
significant changes in CBF or mean BP were observed
between baseline and post-treatment measurements.
DISCUSSION
The premise of this study was that intense noise ex-
posure causes reduced CBF and ischemia, leading to the
production of ROS. The accumulation of ROS then pro-
motes the expression of ICAM-1 to initiate a cascade of
events, which ultimately leads to cochlear damage. ABR
results indicated that noise-induced TTS could be signifi-
cantly attenuated by administering anti-ICAM-1 Ab
intravenously (Fig. 2). This protective effect suggests a
mechanism of inflammatory prevention, whereby anti-
ICAM-1 Ab prevents ICAM-1 from eliciting a deleterious
effect that would otherwise lead to cochlear damage.
Significant data exists showing that ROS promote
the expression of ICAM-1 in endothelial cells and subse-
quently neutrophil-endothelial cell adhesion.6,15 For
example, hydrogen peroxide-induced polymorphonuclear
neutrophil (PMN) adhesion is dependent on the rapid Fig. 3. Auditory threshold shifts (post-noise: 72 hours). Mean audi-
induction of the ICAM-1 mRNA signal and the surface tory threshold shifts of anti-intercellular adhesion molecule-1 anti-
expression of ICAM-1 on the endothelial cell.15 In body (anti-ICAM-1 Ab) (1.25 mg/kg) treatment group rats (dashed
line) exposed to 72 hours of continuous 107 dB sound pressure
addition, hydrogen peroxide-induced expression of level (SPL) broad band noise and control (solid line). Measure-
hyperadhesivity may amplify PMN attachment to the ments were obtained 72 hours following noise exposure at five
endothelium.15 Furthermore, one study demonstrated test frequencies (3, 6, 9, 12, and 18 kHz).
Laryngoscope 000: Month 2009 Seidman et al.: Anti-ICAM-1 Ab and Noise Damage
3
ID: kumarpr I Black Lining: [ON] I Time: 19:21 I Path: //xinchnasjn/01Journals/Wiley/3b2/LARY/Vol00000/080117/APPFile/C2LARY080117

4. J_ID: LARY Customer A_ID: 08-0176.R1 Date: 2-February-09 Stage: Page: 4
cells, but unlike ICAM-1, it is not up regulated by cyto-
kines. ICAM-2 is a ligand for CD11a/CD18 but not for
the other B2-integrins. Another member of the immuno-
globulin superfamily important for leukocyte-endothelial
cell interactions is vascular cell adhesion molecule-1
(VCAM-1), which interacts with the a4b1-integrin
(VLA4) on mononuclear leukocytes. Neutrophils do not
express VLA4. Other members of the immunoglobulin
superfamily such as CD31 and mucosal addressing cell
adhesion molecule-1 (MAdCAM-1) may also contribute to
leukocyte-endothelial cell interactions.
The critical role of ICAM-1 and neutrophil-endothe-
lial cell adhesion in ischemic injury is strengthened,
however, by several studies. Mutant mice that do not
express ICAM-1 are protected against ischemic injury.17
Furthermore, antibodies directed against ICAM-1 have
been shown to protect against ischemic injury.9,17
Another study demonstrated that ICAM-1-deficient and
PMN-depleted mice were relatively resistant to cerebral
ischemia/reperfusion injury.17 Depletion of neutrophils
alone results in protection against ischemia-induced def-
icits in renal function, and although administration of
Fig. 4. Cochlear blood flow (CBF) shifts from a representative ani- anti-ICAM-1 Ab has been found to be protective, it
mal, where the dotted line depicts the 33-minute baseline CBF does not confer protection beyond that observed with
shifts and the solid line depicts CBF shifts following intravenous neutrophil depletion.17 Anti-ICAM-1 Ab added to a
administration of anti-intercellular adhesion molecule-1 antibody
(anti-ICAM-1 Ab) (1.25 mg/kg). The simple spline curve was gener- pulmonary flush and initial reperfusate resulted in a
ated from data points separated by 1-minute intervals. dose-dependent enhancement of the reperfused lung’s
ability to oxygenate blood, possibly as a result of
decreased leukocyte sequestration.18 Thus, it can be con-
cluded that the recruitment of circulating PMN into
3) neutrophil retention was dependent on ICAM-1 and ischemic tissue initially requires the interaction of mi-
oxygen metabolites.6 These results indicate that the crovascular endothelial cells with circulating leukocytes
effect of hydrogen peroxide (i.e., ROS) in instigating neu-
trophil adhesion is mediated by ICAM-1. Utilizing this
knowledge, studies were conducted to show that ROS
scavengers and blockers can attenuate ischemia/reperfu-
sion-induced and noise-induced cochlear damage,4,8
presumably by preventing ROS from inducing the
expression of ICAM-1. Our results suggest that anti-
ICAM-1 Ab has a similar effect in preventing noise-
induced cochlear damage. This effect is mediated by
blocking ICAM-1 and thereby attenuating the inflamma-
tory cascade. Inflammatory damage time course of the
cochlea is consistent with the time courses in other
tissues.16
Although the effect of anti-ICAM-1 Ab attenuates
noise-induced cochlear damage, it was not completely
protective. This may be due to inappropriate concentra-
tion or timing of drug administration or possibly because
other adhesion molecule pathways play a role in noise-
induced hearing loss. ICAM-1 is a single polypeptide
chain (MW ¼ 90 kD) that is glucosulated.17 It has five
immunoglobulin homology domains and is closely related
to neural cell adhesion molecule (NCAM) and myelin-
associated glycoprotein (MAG). The primary sites of
ICAM-1 expression are the microvasculature, peritubu-
lar capillaries, and the vascular endothelium of large Fig. 5. Blood pressure (BP) recording from a representative ani-
vessels. In addition, ICAM-1 is expressed by leukocytes. mal, where the dotted line depicts the 33-minute baseline BP and
the solid line depicts BP following intravenous administration of
ICAM-2, on the other hand, is a glycoprotein of approxi- anti-intercellular adhesion molecule-1 antibody (anti-ICAM-1 Ab
mately 60 kD with only two immunoglobulin-like (1.25 mg/kg). The simple spline curve was generated from data
domains. It is constitutively expressed on endothelial points separated by 1-minute intervals.
Laryngoscope 000: Month 2009 Seidman et al.: Anti-ICAM-1 Ab and Noise Damage
4
ID: kumarpr I Black Lining: [ON] I Time: 19:21 I Path: //xinchnasjn/01Journals/Wiley/3b2/LARY/Vol00000/080117/APPFile/C2LARY080117

5. J_ID: LARY Customer A_ID: 08-0176.R1 Date: 2-February-09 Stage: Page: 5
terrupting the cascade of events that leads to noise-
induced cochlear damage.
Acknowledgments
This research was supported in part by the following
NIH grant: NIDCD-DC00101-05 (MDS); 1R21AT001067-
01-03, NCCAM, July 2003–2005. The authors gratefully
acknowledge the invaluable assistance of Dr. David A.
Komjathy and Francis Leong in the preparation of the
manuscript, and Pharmacia & Upjohn Company for the
gift of anti-ICAM-1 antibody.
BIBLIOGRAPHY
1. Quirk WS, Seidman MD. Cochlear vascular changes in
response to loud noise. Am J Otol 1995;16:322–325.
Fig. 6. Schematic. 2. Lamm K, Arnold W. Noise-induced cochlear hypoxia is in-
tensity dependent, correlates with hearing loss and pre-
cedes reduction of cochlear blood flow. Audiol Neurootol
1996;1:148–160.
3. Thorne PR, Nuttall AL. Laser Doppler measurements of
through specific intercellular adhesion molecules, such cochlear blood flow during loud sound exposure in the
F1 as ICAM-1. guinea pig. Hear Res 1987;27:1–10.
4. Seidman MD, Shivapuja BG, Quirk WS. The protective
Studies have also shown that ICAM-1 plays an im- effects of allopurinol and superoxide dismutase on noise-
portant role in diseases of the head and neck, including induced cochlear damage. Otolaryngol Head Neck Surg
otitis media,10 cholesteatoma,11 inner and middle ear 1993;109:1052–1056.
inflammation,12,19,20 nasal polyposis,21,22 and carcinoma 5. Yamane H, Nakai Y, Takayama M, et al. The emergence of
of the head and neck.13,23 Systemic administration of free radicals after acoustic trauma and strial blood flow.
Acta Otolaryngol Suppl 1995;519:87–92.
anti-ICAM-1 antibody in experimental immune-mediated 6. Linas SL, Whittenburg D, Parsons PE, Repine JE. Ischemia
labyrinthitis showed reduced inflammatory cell infiltra- increases neutrophil retention and worsens acute renal
tion in the scala tympani and the perisaccular tissue of failure: role of oxygen metabolites and ICAM 1. Kidney
the endolymphatic sac.24 Our results depicting the pro- Int 1995;48:1584–1591.
7. Lefer AM, Tsao PS, Lefer DJ, Ma XL. Role of endothelial
tective effect of anti-ICAM-1 Ab on noise-induced TTS dysfunction in the pathogenesis of reperfusion injury af-
imply that ICAM-1 also plays a role in noise-induced ter myocardial ischemia. FASEB J 1991;5:2029–2034.
cochlear damage. 8. Yamasoba T, Nuttall AL, Harris C, Raphael Y, Miller JM.
Our results indicate that pretreatment with anti- Role of glutathione in protection against noise-induced
ICAM-1 Ab following noise exposure followed with a hearing loss. Brain Res 1998;784:82–90.
9. Bonventre JV, Kelly KJ. Adhesion molecules and acute
booster dose 24 hours afterwards may reduce noise- renal failure. Adv Nephrol Necker Hosp 1996;25:159–
induced hearing loss without altering CBF or mean BP. 176.
However, its long-term effectiveness is not clear and needs 10. Sone M, Russlie HQ, Canafax DM, Paparella MM. Expres-
further investigation. Many other important issues also sion of intercellular adhesion molecule-1 in rat inner ear
due to bacterial otitis media. Ann Otol Rhinol Laryngol
need to be addressed. For example, what effect does anti- 1999;108:648–652.
ICAM-1 Ab have on cochlear histology? Is ICAM-1 11. Shinoda H, Huang CC. Localization of intercellular adhe-
expressed during noise exposure or after noise exposure or sion molecule-1 in middle ear cholesteatoma. Eur Arch
both? It is also important to determine if anti-ICAM-1 Ab Otorhinolaryngol 1995;252:385–390.
could prevent the degeneration of hair cell, if it were given 12. Pawankar R, Tomiyama S, Jinnouchi K, Ikezono T, Nonaka
M, Yagi T. Intercellular adhesion molecule-1 expression
after a traumatic noise exposure. What is the optimal in the inner ear of rats following secondary immune reac-
treatment window following noise exposure? Lastly, the tion in the endolymphatic sac. Acta Otolaryngol Suppl.
optimal dose of anti-ICAM-1 Ab needs to be determined. 1998;539:5–14.
Clearly, additional studies are necessary to determine if 13. Wollenberg B, Jan N, Sautier W, Hofmann K, Schmitt UM,
Stieber P. Serum levels of intercellular adhesion mole-
anti-ICAM-1 Ab represents a possible therapeutic cule-1 in squamous cell carcinoma of the head and neck.
approach to noise-induced hearing loss. Tumour Biol 1997;18:88–94.
14. Shirwany NA, Seidman MD, Tang W. Effect of transtym-
panic injection of steroids on cochlear blood flow, auditory
sensitivity, and histology in the guinea pig. Am J Otol
1998;19:230–235.
CONCLUSION 15. Lo SK, Janakidevi K, Lai L, Malik AB. Hydrogen peroxide-
Intravenous administration of anti-ICAM-1 Ab sig- induced increase in endothelial adhesiveness is depend-
nificantly attenuates noise-induced TTS and has no ent on ICAM-1 activation. Am J Otol 1993;264:
L406–L412.
significant effect on CBF and mean BP. These results 16. Gloddek B, Bodmer D, Brors D, Keithley EM, Ryan AF.
support our earlier conclusions, which demonstrate the Induction of MHC class ii antigens on cells of the inner
protective effects of ROS scavengers and blockers in in- ear. Audiol Neurootol 2002;7:317–323.
Laryngoscope 000: Month 2009 Seidman et al.: Anti-ICAM-1 Ab and Noise Damage
5
ID: kumarpr I Black Lining: [ON] I Time: 19:21 I Path: //xinchnasjn/01Journals/Wiley/3b2/LARY/Vol00000/080117/APPFile/C2LARY080117

6. J_ID: LARY Customer A_ID: 08-0176.R1 Date: 2-February-09 Stage: Page: 6
17. Springer TA. Adhesion receptors of the immune system. 22. Olejniczak I, Kobos J, Gryczynski M, Durko M, Pietruszewska
Nature 1990;346:425–434. W. Expression of adhesion molecule ICAM-1 in patients
18. Buchanan SA, Mauney MC, deLima NF, et al. Enhanced with nasal polyps [in Polish]. Otolaryngol Pol 2007;61:
isolated lung function after ischemia with anti-intercellu- 607–611.
lar adhesion molecule antibody. J Thorac Cardiovasc 23. Shirai, A, Furukawa M, Yoshizaki T. Expression of intercel-
Surg 1996;111:941–947. lular adhesion molecule (ICAM)-1 in adenoid cystic carci-
19. Suzuki M, Harris JP. Expression of intercellular adhesion noma of the Head and Neck. Laryngoscope 2003;113:
molecule-1 during inner ear inflammation. Ann Otol Rhi- 1955–1960.
nol Laryngol 1995;104:69–75. 24. Soriano SG, Lipton SA, Wang YF, et al. Intercellular adhe-
20. Wang SZ, Chen ZC, McNamar JP, Wang SY, Cheng QF. The sion molecule-1-deficient mice are less susceptible to cere-
relationship between the protective effect of amifostine bral ischemia-reperfusion injury. Ann Neurol 1996;39:
and decreased intercellular adhesion molecule 1 expres- 618–624.
sion. Am J Otolaryngol 2005;26:118–22. 25. Kelly KJ, Tolkoff-Rubin NE, Rubin RH, et al. An oral plate-
21. Zhou B, Han D, Liu Z. Role of ICAM-1 in eosinophilia and let-activating factor antagonist, Ro-24-4736, protects the
prognosis of nasal polyps. Lin Chuang Er Bi Yan Hou Ke rat kidney from ischemic injury. Am J Physiol 1996;271:
Za Zhi 2004;18:72–73. F1061–F1067.
Laryngoscope 000: Month 2009 Seidman et al.: Anti-ICAM-1 Ab and Noise Damage
6
ID: kumarpr I Black Lining: [ON] I Time: 19:21 I Path: //xinchnasjn/01Journals/Wiley/3b2/LARY/Vol00000/080117/APPFile/C2LARY080117