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Tear Tryptase in Vernal Keratoconjunctivitis
Khalid F. Tabbara, MD
Arch Ophthalmol. 2001;119:338-342.
ABSTRACT
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Objectives To determine the tear level of tryptase (a marker of mast cell activation)
in vernal keratoconjunctivitis (VKC) before and after treatment. In addition,
eosinophil counts in conjunctival scrapings and ocular surface temperature
before and after treatment were studied.
Patients and Methods A total of 20 patients, 7 years or older with VKC, were included in
this study. Tear samples for tryptase determination were collected before
and 2 weeks after treatment with 4% disodium cromoglycate eyedrops and 0.1%
fluorometholone eyedrops. In addition, conjunctival scrapings were obtained
for microscopic evaluation, and measurement of the ocular surface temperature
was performed before and 2 weeks after treatment. One patient was excluded
because the patient did not receive topical treatment. Control tear samples
were collected from 20 normal control patients for tryptase determination.
Results There were 19 patients with VKC (17 males, 2 females). The age range
was 7 to 17 years with a mean age of 9 years. The mean number of eosinophils
prior to initiation of therapy was 11.37 eosinophils with a range of 1 to
34 per high-power field. Following treatment, the mean number of eosinophils
was 3.42 eosinophils per high-power field with a range of 0 to 11 (P<.01). The mean ocular surface temperature for the right eye before
treatment was 35.56°C (range, 34.46°C-36.50°C) and after treatment
was 33.53°C (range, 31.13°C-35.40°C). For the left eye, the mean
ocular surface temperature before treatment was 35.49°C (range, 34.86°C-36.16°C)
and after treatment was 33.88°C (range, 32.40°C-35.53°C). The
ocular surface temperature was found to decrease significantly following treatment
(P<.001). The levels of tryptase in tears of patients
with VKC were determined before and after treatment. The mean level was 16.77
ng/mL (range, <5-115 ng/mL). Following treatment with topical 4% disodium
cromoglycate and 0.1% fluorometholone eyedrops, the mean level of tryptase
decreased to 7.29 ng/mL (range, <5-44.1 ng/mL) (P<.05).
Conclusions Patients with severe VKC had high levels of tryptase in tears. Following
treatment, the level of tryptase in tears decreased significantly.
INTRODUCTION
VERNAL keratoconjunctivitis (VKC) is a form of chronic allergic conjunctivitis
that is potentially blinding by the complications of the disease or by the
long-term use and abuse of topical corticosteroids. Patients with VKC have
an increase in the number of eosinophils, mast cells, and other inflammatory
cells in the conjunctiva. The diagnosis of ocular allergy in most cases remains
clinical. There are no specific and sensitive diagnostic assays for ocular
allergy. Tryptase is a neutral protease that has been shown to selectively
concentrate in the granules of human mast cells. It is well known that mast
cells play a pivotal role in the pathogenesis of VKC. Determination of granule
products of mast cells in tears of patients with allergic conjunctivitis may
reflect the degree of activation of the mast cell.1-4
The release of tryptase in tears may serve as a clinical marker for mast cell
activation and for monitoring of ocular allergy following treatment. Recent
studies have shown that mast cells have structural and functional heterogeneity.5-7
The distribution and concentration of human tryptase–positive,
chymase–negative mast cells and tryptase– and chymase–positive
mast cells were examined in the conjunctival biopsy specimens of patients
with VKC, giant papillary conjunctivitis, allergic conjunctivitis, and asymptomatic
soft contact lens wearers as well as normal control individuals.5
Epithelial mast cells were found in all cases of VKC specimens. Activation
of these epithelial mast cells may lead to an increase in tear tryptase levels.
Most cells were mast cells and tryptase-positive, chymase-negative cells.
In subjects with VKC, the number of mast cells (tryptase-positive, chymase-negative)
was much higher in the epithelial cells than in the substantia propria. Furthermore,
adhesion molecules, intercellular adhesion molecule-1, were shown to be induced
and expressed on epithelial cells of patients with VKC.8
Tryptase seems to be a sensitive and specific marker of type I hypersensitivity
reaction and anaphylaxis.1, 9-17
It is conceded that search for a safe, simple, sensitive, and specific diagnostic
test for ocular allergy and for the monitoring of the severity of ocular allergy
is highly desirable. The main objective of this study was to determine the
tear levels of tryptase in patients with VKC before and after treatment.
PATIENTS, MATERIALS, AND METHODS
PATIENTS
Following a minimum washout period of 1 week, 20 patients (18 males,
2 females), 7 years or older with VKC were included in this study. In addition,
a control group of 20 age- and sex-matched patients with no history of atopic
disorders and no allergic conjunctivitis was included. The protocol was approved
by the institution research council, and consent was obtained from each patient's
guardian. One patient was excluded because of discontinuation of topical medications.
Patients who were known to be sensitive to topical medications or have secondary
infection were excluded before selection. Contact lens wearer were not included
in this study. A Schirmer test was performed before and after treatment. Nineteen
of 20 patients and 20 control patients had collection of unstimulated tear
samples with capillary tubes before and 2 weeks after treatment. Tears and
serum samples were collected to determine levels of tryptase among the patients
and controls. The ocular surface temperature was measured before and 2 weeks
after treatment.
CLINICAL EXAMINATION
The demographic data for each patient were recorded. The patient's medical
history was documented. Medications administered topically or systemically
were recorded. A subjective assessment of symptoms was recorded. Physical
examinations were conducted by the investigator. The diagnosis of VKC and
the grading of signs were made according to the criteria for the diagnosis
of VKC previously reported.18 Clinical signs
of ocular allergy were assessed and recorded. Patients underwent slitlamp
examination. Fluorescein staining of the external eye was assessed. The signs
of ocular allergy, including conjunctival hyperemia, edema, punctate keratitis,
and Trantas dots, were recorded. The temperature of the temporal bulbar conjunctival
surface was recorded before and 2 weeks after treatment. The following signs
were assessed: hyperemia, papillary hypertrophy, punctate keratitis, and Trantas
dots. Hyperemia and papillary hypertrophy were graded as follows: 0, none;
1+, mild; 2+, moderate; and 3+, severe. Punctate keratitis was graded as follows:
0, none; 1+, 1 quadrant of punctate keratitis; 2+, 2 quadrants of punctate
keratitis; and 3+, 3 or more quadrants of punctate keratitis. Trantas dots
were graded as follows: 0, no evidence of dots; 1+, 1 to 2 dots; 2+, 3 to
4 dots; and 3+, more than 4 dots. Cases of VKC with a score of 3 or less were
graded mild, more than 3 but less than 6 were considered moderate, and more
than 6 were considered severe.
LABORATORY DIAGNOSIS AND DETERMINATION OF TRYPTASE IN TEARS
Blood was collected for determination of tryptase before treatment.
Two microliters of unstimulated tear fluid collected with capillary tubes
were subjected to the determination of tryptase concentration.16-18
Unstimulated tear samples were collected with a capillary tube from 19 patients
and 20 controls before and after treatment and stored at -20°C until
an assay was performed. The UniCAP 100 instrument (Pharmacia, Upsala, Sweden)
with built-in software was used to process all steps of tryptase assay. The
values were expressed in nanograms per milliliter. The detection limit was
0.5 ng/mL. Antitryptase, covalently coupled to Immuno CAP (Pharmacia), reacted
with tryptase in the patient specimen. After washing enzyme-labeled antibodies
against tryptase, a complex was formed. After incubation, unbound enzyme antitryptase
was washed away, and the bound complex was then incubated with a developing
agent. After stopping the reaction, the fluorescence in the eluate was measured.
The higher the fluorescence value found, the more tryptase was present in
the fluid. Following therapy, tryptase assessment in tears was carried out
in a random fashion. Tryptase levels in tears were determined 2 weeks following
treatment.
MEASUREMENT OF OCULAR SURFACE TEMPERATURE
The ocular surface temperature was measured by a probe (First Temp Genius
Model 3000A, Tympanic Thermometer; Sherwood Medical Industries Ltd, West Sussex,
England) in each visit. The temperature was measured over the temporal portion
of the bulbar conjunctiva without anesthesia. Three measurements were obtained,
and the mean was recorded at a room temperature of 21°C. The temperature
reading was the mean of 3 readings before treatment and 3 readings after treatment.
CONJUNCTIVAL SCRAPINGS AND TREATMENT
Conjunctival scrapings were obtained before and 2 weeks after treatment.
Following instillation of topical anesthetic eyedrops in each eye, the conjunctival
scrapings were obtained and placed onto glass slides, fixed with absolute
methanol, and stained with Giemsa stain to assess the number of eosinophils
per 10 high-power field (HPF). Each patient was given 1 drop of 4% disodium
cromoglycate and 1 drop of 0.1% fluorometholone in both eyes 4 times daily
for 2 weeks. One patient did not receive the topical medications and was excluded
from the study.
A paired t test or nonparametric counterpart
analysis was used to compare the pretreatment and posttreatment levels of
tryptase, ocular surface temperature, and eosinophil values. P<.05 was considered significant.
RESULTS
A total of 19 patients were included in this study (17 males and 2 females).
The age range was 7 to 17 years with a mean age of 9 years. Three patients
had mild degree of VKC, 7 patients had moderate VKC, and 9 patients had severe
VKC. The mean number of eosinophils prior to initiation of therapy was 11.37
with a range of 1 to 34 per HPF. Following treatment, the mean number of eosinophils
was 3.42 per HPF with a range of 0 to 11. The mean number of eosinophils in
the conjunctival scraping decreased significantly (P<.01)
after treatment. Table 1 gives
the mean ocular surface temperature of each patient before and 2 weeks after
initiation of treatment. The mean ocular surface temperature for the right
eye before treatment was 35.56°C (range, 34.46°C-36.50°C) and
after treatment was 33.53°C (range, 31.13°C-35.40°C). For the
left eye, the mean ocular surface temperature before treatment was 35.49°C
(range, 34.86°C-36.16°C) and after treatment was 33.88°C (range,
32.40°C-35.53°C). There was a statistically significant decrease (P<.001) in the ocular surface temperature after treatment,
which correlated with the decrease in conjunctival hyperemia following topical
therapy. Table 2 gives the tryptase
levels in tears before and after treatment in patients with VKC. The mean
tryptase level in tears in patients with VKC was 16.77 ng/mL before treatment
and 7.29 ng/mL after treatment. The range of tear tryptase levels in severe
VKC was 5.2 to 115 ng/mL before treatment and <5 to 44.1 ng/mL after treatment
(P<.05). The level of tryptase correlated with
the severity score of VKC. In the control group, the tear tryptase level was
<5 ng/mL in all tear samples. The mean serum level of tryptase in patients
with VKC was 6.3 ng/mL (range, 3.9-8.4 ng/mL). The mean serum tryptase level
in the control group was 6.8 ng/mL (range, 5.6 ng/mL-13.5 ng/mL). The serum
level of tryptase in patients with VKC was within normal limits and similar
to the general population despite the elevation in the tears tryptase.
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Table 1. Mean Ocular Surface Temperature Before and After Treatment
Among Patients With Vernal Keratoconjunctivitis (VKC)
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Table 2. Tryptase Levels in Tears Before and After Treatment Among
Patients With Vernal Keratoconjunctivitis (VKC)
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COMMENT
In most cases of ocular allergy, the diagnosis is clinical. This study
aimed to find a sensitive and specific test for the diagnosis and determination
of treatment efficacy in ocular allergy. The ocular surface temperature was
assessed before and after treatment. Conjunctival temperature of patients
with VKC was decreased significantly following therapy. In this study, there
was a statistically significant decrease in ocular surface temperature after
treatment. Ocular surface temperature measurement is a helpful objective indicator
for monitoring improvement in ocular allergy. The ocular surface temperature
may be a simple, accurate, objective, and sensitive method for the assessment
of the prognosis of patients with ocular allergy receiving topical therapy.
Eosinophils are known to be major indicators of ocular allergy. They
are known to contribute to the ocular surface toxic effects by the secretion
of their granules and cytokines such as eosinophilic major basic protein,
eosinophilic peroxidase, eosinophilic cationic protein, and neurotoxic proteins.
The number of eosinophils was assessed before and after therapy. The number
of eosinophils in the conjunctival scrapings specimens showed a decrease in
number after treatment. This decrease in the number of eosinophils correlated
with the improvement in VKC.
Tryptase is a neutral protease that is selectively concentrated in the
secretory granules of human mast cells. Tryptase is released into the ocular
surface following the degranulation of the mast cell. In this study, the enzyme-linked
immunosorbent assay (ELISA) method was carried out for the detection of tryptase
in tears. The sensitivity of this new immunoassay has been previously described
by Schwartz et al12 who reported the mean level
of serum tryptase in healthy subjects. The level of tear tryptase may be indicative
of the exacerbation of ocular allergy. Tryptase in tears seems to be a sensitive
assay for the diagnosis of severe forms of VKC and for monitoring the response
to treatment.
The release of tryptase into the mucosal surfaces as well as into the
circulation serves as a clinical marker of mast cell activation. The current
study describes an ELISA method utilizing a newly developed monoclonal antibody
for the capture of an epitope in the tryptase in both the serum and tears.
In this study, tryptase was found as a sensitive clinical indicator of mast
cell activation, and the level of tryptase in tears correlated with the severity
of the disease. Increased levels of tryptase were found in patients with severe
forms of VKC. The increase in tear tryptase was not associated with an increase
in serum tryptase. Tryptase is released from the human mast cell granules
on degranulation. Amounts of tryptase less than 1% of those in mast cells
have been detected in basophils, but none has been detected in other cell
types found in normal human tissues and blood. A tryptase, therefore, is a
sensitive indicator of mast cell activity, a cell that plays an important
role in the pathogenesis of VKC. The level of tryptase in tears was found
to be markedly increased in patients with severe VKC. Following treatment,
the level of tryptase decreased significantly in tear fluids of patients with
VKC. The determination of mast cell activation in ocular allergy can be substantially
improved by measurements of tryptase in tears in patients with VKC. The amounts
of tryptase released by mast cells during mild, moderate, and severe allergic
conjunctivitis may vary and seems to correlate with the severity of the disease.
Tear tryptase levels showed considerable individual variability (Table 2). In 3 cases, the tear levels of
tryptase increased following treatment secondary to exacerbation of allergic
conjunctivitis and due to treatment failure. All 3 patients, numbers 8, 10,
and 17, had worsening of their signs and symptoms following treatment and
showed an increase in the tear tryptase levels.
The tryptase levels in the serum correlated closely with the drop in
the mean arterial pressure19 of patients who
had insect-sting induced anaphylaxis. Similar situations of anaphylaxis have
been reported, and the severity of the allergic response did correlate with
the tryptase level in the serum.14, 19-20
On the other hand, instances of food-induced anaphylaxis21
show no elevation, suggesting a mechanism that does not involve mast cell
activation. Levels of tryptase in bronchoalveolar lavage fluid,3, 16, 22-24
skin chamber fluid,25-27
and nasal fluid4, 28-29
have been used to assess mast cell activation in allergic conditions. Butrus
et al30 described increased levels of tryptase
in human tears of patients with allergic conjunctivitis. Although the measurement
of tryptase in ocular fluids has obvious clinical utilization, the major deficiency
with many of the current methods for measurements is sensitivity. The assay
used in this study seems to be a sensitive and specific method for measurements
of tryptase to assess mast cell activation in ocular allergy. Repeated freezing
and thawing of samples did not seem to affect immunoreactivity.12
The immunoassay for the determination of tryptase in tears can be performed
in less than 1 hour, raising a possibility that tryptase levels could be used
to monitor the therapy and disposition of patients in urgent clinical situations.
Schwartz et al12 have reported that serum levels
of tryptase in normal subjects range from 1.9 to 4.9 ng/mL. It is likely that
the baseline level of tryptase reflects some combination of the total mast
cell burden and the rate of mast cell turnover as well as the magnitude of
spontaneous subclinical activation of mast cells. It has been shown that minimal
variation of tryptase in healthy individuals may be demonstrated. On the other
hand, the baseline level of tryptase in healthy subjects seems to be constant
over a period of months or years.12 Certain
healthy individuals may have a baseline serum tryptase level of 10 ng/mL or
higher. It is not known whether this apparent increase indicates an increase
of population of sensitized mast cells or an alternative mechanism for the
hyperresponsive state of that individual.
The mean concentration of tryptase in serum was not increased in this
patient population, although the tryptase level in tears was increased. This
suggests that a localized allergy at a target organ may be too small to increase
the serum level of tryptase, and this indicates that these patients have a
localized allergy such as VKC without having systemic disease. Rasp et al10 found that the mean concentration of tryptase in
serum was not significantly different from normal controls and subjects with
active allergic rhinitis, despite elevated levels of tryptase being present
in the nasal fluids. The results obtained by Rasp and associates are similar
to what was found in this study, where patients with VKC had elevated levels
of tryptase in tears without an increase of levels in serum. This shows that
the absolute level of tryptase in the circulation does not reflect regional
mast cell activation, which is limited to a local tissue site. In certain
instances tear samples collected at baseline and at 15 and 60 minutes after
the onset of clinical response may show at least a 2-fold elevation in tryptase,
providing a greater sensitivity for detecting mast cell activation than examination
of a single tryptase sample. In certain clinical situations, however, this
is not possible unless if the patient had a level of tryptase determined prior
to the onset of the allergic process. It seems that the relative increase
in tryptase is a more sensitive indicator of mast cell involvement than the
absolute level of tryptase.
In summary, a new immunoassay for tryptase determination in tears has
been shown to be sensitive in the detection of tryptase levels in tears. The
tryptase level at baseline of patients with VKC may reflect the local responsiveness
of the mast cell activation. Following therapy, there was marked decrease
in the level of tryptase in tears, which correlated with the improvement in
the clinical signs and symptoms. Tryptase levels in tears may serve as a good
diagnostic tool for ocular allergy and for monitoring of activity of the disease.
AUTHOR INFORMATION
Accepted for publication August 5, 2000.
The study was supported in part by the Eye Center and the Eye Foundation
for Research in Ophthalmology, Riyadh.
I would like to thank the administrator of the Eye Center, Najwa Tabbara,
for her help and support, and Vangie Ontoria for outstanding secretarial assistance.
I also thank Ehab Hammouda for performing the microbiology procedures, Bashir
A. Khan, PhD, Biomedical Statistician, Biomedical Statistics and Scientific
Computing Department, King Faisal Specialist Hospital and Research Centre,
Riyadh, for performing the statistical analysis, and Harb Al Harfi, MD, National
Center of Allergy, Department of Asthma & Immunology, for his helpful
suggestions.
Corresponding author and reprints: Khalid F. Tabbara, MD, PO Box
55307, Riyadh 11534, Saudi Arabia (e-mail: k.tabbara{at}nesma.net.sa).
From the Department of Ophthalmology, College of Medicine, King Saud
University, and The Eye Center, The Eye Foundation for Research in Ophthalmology,
Riyadh, Saudi Arabia. I have no proprietary interest in any of the materials
used in this study.
REFERENCES
| |
1. Ansari MQ, Zamora JL, Lipscomb MF. Postmortem diagnosis of acute anaphylaxis by serum tryptase analysis:
a case report. Am J Clin Pathol. 1993;99:101-103.
ISI
| PUBMED
2. Broide DH, Gleich GJ, Cuomo AJ, et al. Evidence of ongoing mast cell and eosinophil degranulation in symptomatic
asthma airway. J Allergy Clin Immunol. 1991;88:637-648.
FULL TEXT
|
ISI
| PUBMED
3. Castells M, Schwartz LB. Tryptase levels in nasal-lavage fluid as an indicator of the immediate
allergic response. J Allergy Clin Immunol. 1988;82:348-355.
FULL TEXT
|
ISI
| PUBMED
4. Enander I, Matsson P, Nystrand J, et al. A new radioimmunoassay for human mast cell tryptase using monoclonal
antibodies. J Immunol Methods. 1991;138:39-46.
FULL TEXT
|
ISI
| PUBMED
5. Irani AM, Butrus SI, Tabbara KF, Schwartz LB. Human conjunctival mast cells: distribution of MCT, MCTC in vernal conjunctivitis and giant papillary conjunctivitis. J Allergy Clin Immunol. 1990;86:34-40.
FULL TEXT
|
ISI
| PUBMED
6. Irani A-MA, Bradford TR, Kepley CL, Schechter NM, Schwartz LB. Detection of MCT and MCTC types of human mast
cells by immuno-histochemistry using new monoclonal anti-tryptase and anti-chymase
antibodies. J Histochem Cytochem. 1989;37:1509-1515.
FREE FULL TEXT
7. Irani AA, Schechter NM, Craig SS, DeBlois G, Schwartz LB. Two types of human mast cells that have distinct neutral protease compositions. Proc Natl Acad Sci U S A. 1986;83:4464-4468.
FREE FULL TEXT
8. Tabbara KF, Al Kharashi SA. Efficacy of nedocromil 2% versus fluorometholone 0.1%: a randomized,
double-masked trial comparing the effects on severe vernal keratoconjunctivitis. Br J Ophthalmol. 1999;83:180-184.
FREE FULL TEXT
9. Miller JS, Westin EH, Schwartz LB. Cloning and characterization of complementary DNA for human tryptase. J Clin Invest. 1989;84:1188-1195.
10. Rasp G, Hochstrasser K. Tryptase in nasal fluid is a useful marker of allergic rhinitis. Allergy. 1993;48:72-74.
ISI
| PUBMED
11. Schwartz LB, Bradford TR, Rouse C, et al. Development of a new, more sensitive immunoassay for human tryptase:
use in systemic anaphylaxis. J Clin Immunol. 1994;14:190-204.
FULL TEXT
|
ISI
| PUBMED
12. Schwartz LB, Metcalfe DD, Miller JS, Earl H, Sullivan T. Tryptase levels as an indicator of mast-cell activation in systemic
anaphylaxis and mastocytosis. N Engl J Med. 1987;316:1622-1626.
ABSTRACT
13. Schwartz LB, Yunginger JW, Miller JS, Bokhari R, Dull D. The time course of appearance and disappearance of human mast cell
tryptase in the circulation after anaphylaxis. J Clin Invest. 1989;83:1551-1555.
14. Schwartz LB, Bradford TR. Regulation of tryptase from human lung mast cells by heparin: stabilization
of the active tetramer. J Biol Chem. 1986;261:7372-7379.
FREE FULL TEXT
15. Walls AF, Bennett AR, Godfrey RC, Holgate ST, Church MK. Mast cell tryptase and histamine concentrations in bronchoalveolar
lavage fluid from patients with interstitial lung disease. Clin Sci. 1991;81:183-188.
PUBMED
16. Watkins J. Tryptase release and clinical severity of anaesthetic reactions. Agents Actions. 1992;36(suppl C):C203-C205.
17. Wenzel S, Irani AM, Sanders JM, Bradford TR, Schwartz LB. Immunoassay of tryptase from human mast cells. J Immunol Methods. 1986;86:139-142.
FULL TEXT
|
ISI
| PUBMED
18. Bleik JH, Tabbara KF. Topical cyclosporine in vernal conjunctivitis. Ophthalmology. 1991;98:1679-1684.
ISI
| PUBMED
19. Van der Linden PG, Hack CE, Poortman J, Vivié-Kipp YC, Struyvenberg A, Van der Zwan JK. Insect-sting challenge in 138 patients: relation between clinical severity
of anaphylaxis and mast cell activation. J Allergy Clin Immunol. 1992;90:110-118.
ISI
| PUBMED
20. Matsson P, Enander I, Andersson A-S, Nystrand J, Schwartz L, Watkins J. Evaluation of mast cell activation (tryptase) in two patients suffering
from drug-induced hypotensoid reactions. Agents Actions. 1991;33:218-220.
FULL TEXT
|
ISI
| PUBMED
21. Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and
adolescents. N Engl J Med. 1992;327:380-384.
ABSTRACT
22. Wenzel SE, Fowler III AA, Schwartz LB. Activation of pulmonary mast cells by bronchoalveolar allergen challenge:
in vivo release of histamine and tryptase in atopic subjects with and without
asthma. Am Rev Respir Dis. 1988;137:1002-1008.
ISI
| PUBMED
23. Broide DH, Eisman S, Ramsdell JW, Ferguson P, Schwartz LB, Wasserman SI. Airway levels of mast cell-derived mediators in exercise-induced asthma. Am Rev Respir Dis. 1990;141:563-568.
ISI
| PUBMED
24. Calhoun WJ, Swensen CA, Dick EC, Schwartz LB, Lemanske RF Jr, Busse WW. Experimental rhinovirus 16 infection potentiates histamine release
following antigenbroncho-provocationing allergic subjects. Am Rev Respir Dis. 1991;144:1267-1273.
ISI
| PUBMED
25. Schwartz LB, Atkins PC, Bradford TR, Fleekop P, Shalit M, Zweiman B. Release of tryptase together with histamine during the immediate cutaneous
response to allergen. J Allergy Clin Immunol. 1987;80:850-855.
ISI
| PUBMED
26. Shalit M, Schwartz LB, von Allmen C, Atkins PC, Lavker RM, Zweiman B. Release of histamine and tryptase during continuous and interrupted
cutaneous challenge with allergen in humans. J Allergy Clin Immunol. 1990;86:117-125.
FULL TEXT
|
ISI
| PUBMED
27. Atkins PC, Schwartz LB, Adkinson NF, von Allmen C, Valenzano M, Zweiman B. In vivo antigen-induced cutaneous mediator release: simultaneous comparisons
of histamine, tryptase, and prostaglandin D2 release and the effect
of oral corticosteroid administration. J Allergy Clin Immunol. 1990;86:360-370.
FULL TEXT
|
ISI
| PUBMED
28. Juliusson S, Holmberg K, Baumgarten CR, Olsson M, Enander I, Pipkorn U. Tryptase in nasal lavage fluid after local allergen challenge: relationship
to TAME-esterase activity. Allergy. 1991;46:459-465.
ISI
| PUBMED
29. Proud D, Bailey GS, Naclerio RM, et al. Tryptase and histamine as markers to evaluate mast cell activation
during the responses to nasal challenge with allergen, cold, dry air, and
hyperosmolar solutions. J Allergy Clin Immunol. 1992;89:1098-1110.
FULL TEXT
|
ISI
| PUBMED
30. Butrus SI, Ochsner KI, Abelson MB, Schwartz LB. The level of tryptase in human tears: an indicator of activation of
conjunctival mast cells. Ophthalmology. 1990;97:1678-1683.
ISI
| PUBMED
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