Abstract
Tryptase, a neutral protease, is selectively concentrated in the secretory granules of human mast cells, and its release into the circulation serves as a clinical marker of mast cell activation. The current study describes a new, more sensitive ELISA utilizing a newly developed, mouse monoclonal IgG1 antibody for capture called B12 and capable of detecting tryptase in normal plasma and serum. The greater sensitivity of the new immunoassay results in part from a greater portion of tryptase being detected. Mean levels of tryptase in serum from normal subjects from Richmond, Virginia (4.9 ng/ml;n=56), Munich, Germany (3.8 ng/ml;n=19), and Amersfoort, The Netherlands (1.9 ng/ml;n=8) were as indicated. In 62 subjects with ongoing allergic rhinitis, tryptase levels were no different in serum than for 19 normal controls, indicating that local mast cell activation is not necessarily reflected in the circulation. In 61 subjects sensitive to honey bee or yellow jacket venom by history, the 17 destined to have a severe, hypotensive response to a sting challenge had higher levels of tryptase at baseline than mild reactors, nonreactors, and controls, suggesting that baseline levels of tryptase may predict the severity of the clinical response to allergen in sensitive subjects.
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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 316:1622–1626, 1987
Schwartz LB, Huff TF: Biology of mast cells and basophils.In Allergy: Principals and Practice, E Middleton, Jr., CE Reed, EF Ellis, NF Adkinson, Jr., JW Yunginger, WW Busse (eds). St. Louis, Mosby-Year Book, 1993, pp 135–168
Schwartz LB, Austen KF: Acid hydrolases and other enzymes of rat and human mast cell secretory granules. KROC Found Ser 14:103–121, 1981
Castells MC, Irani AM, Schwartz LB: Evaluation of human peripheral blood leukocytes for mast cell tryptase. J Immunol 138:2184–2189, 1987
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 83:1551–1555, 1989
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 90:110–118, 1992
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 33:218–220, 1991
Silvers WS, Essember LJ, Williams PB, Selner JC, Dolen WK: Anaphylaxis due to diclofenac sodium (Voltaren): Evidence of mast cell mediator release. Immunol Allergy Pract 13:193–196, 1991
Yunginger JW, Nelson DR, Squillace DL, Jones RT, Holley KE, Hyma BA, Biedrzycki L, Sweeney KG, Sturner WQ, Schwartz LB: Laboratory investigation of deaths due to anaphylaxis. J Forens Sci 36:857–865, 1991
Ownby DR: Anaphylaxis associated with latex allergy during barium enema examinations. Am J Roentgen 156:903–908, 1991
Watkins J: Tryptase release and clinical severity of anaesthetic reactions. Agents Actions 36 (Suppl C):C203-C205, 1992
Laroche D, Lefrançois C, Gérard J-L, Dubois F, Vergnaud M-C, Guéant J-L, Bricard H: Early diagnosis of anaphylactic reactions to neuromuscular blocking drugs. Br J Anaesth 69:611–614, 1992
Ansari MQ, Zamora JL, Lipscomb MF: Postmortem diagnosis of acute anaphylaxis by serum tryptase analysis: A case report. Am J Clin Pathol 99:101–103, 1993
Sampson HA, Mendelson L, Rosen JP: Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med 327:380–384, 1992
Wenzel SE, Fowler AA, 3d., 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 Resp Dis 137:1002–1008, 1988
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 Resp Dis 141:563–568, 1990
Calhoun WJ, Swensen CA, Dick EC, Schwartz LB, Lemanske RF, Jr., Busse WW: Experimental rhinovirus 16 infection potentiates histamine release following antigen bronchoprovocation in allergic subjects. Am Rev Resp Dis 144:1267–1273, 1991
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 81:183–188, 1991
Bousquet J, Chanez P, Lacoste JY, Enander I, Venge P, Peterson C, Ahlstedt S, Michel F-B, Godard P: Indirect evidence of bronchial inflammation assessed by titration of inflammatory mediators in BAL fluid of patients with asthma. J Allergy Clin Immunol 88:649–660, 1991
Broide DH, Gleich GJ, Cuomo AJ, Coburn DA, Federman EC, Schwartz LB, Wasserman SI: Evidence of ongoing mast cell and eosinophil degranulation in symptomatic asthma airway. J Allergy Clin Immunol 88:637–648, 1991
Sedgwick JB, Calhoun WJ, Gleich GJ, Kita H, Abrams JS, Schwartz LB, Volovitz B, Ben-Yaakov M, Busse WW: Immediate and late airway response of allergic rhinitis patients to segmental antigen challenge: Characterization of eosinophil and mast cell mediators. Am Rev Resp Dis 144:1274–1281, 1991
Broudy VC, Lin N, Zsebo KM, Birkett NC, Smith KA, Bernstein ID, Papayannopoulou T: Isolation and characterization of a monoclonal antibody that recognizes the humanc-kit receptor. Blood 79:338–346, 1992
Jarjour NN, Calhoun WJ, Stevens CA, Salisbury SM: Exercise-induced asthma is not associated with mast cell activation or airway inflammation. J Allergy Clin Immunol 89:60–68, 1992
Ferguson AC, Whitelaw M, Brown H: Correlation of bronchial eosinophil and mast cell activation with bronchial hyperresponsiveness in children with asthma. J Allergy Clin Immunol 90:609–613, 1992
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 80:850–855, 1987
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 86:117–125, 1990
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 86:360–370, 1990
Deleuran B, Kristensen M, Larsen CG, Matsson P, Enander I, Andersson A-S, Thestrup-Pedersen K: Increased tryptase levels in suction-blister fluid from patients with urticaria. Br J Dermatol 125:14–17, 1991
Tsubaki T, Iikura Y, Saito H, Akasawa A, Tabana T, Matsuda S, Koshibu T, Iwasaki A, Obata T, Sugihara Y: Changes in histamine/tryptase levels in skin chambers: Application for clinical evaluation of atopic dermatitis. Int Arch Allergy Immunol 99:459–462, 1992
Castells M, Schwartz LB: Tryptase levels in nasal-lavage fluid as an indicator of the immediate allergic response. J Allergy Clin Immunol 82:348–355, 1988
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 46:459–465, 1991
Proud D, Bailey GS, Naclerio RM, Reynolds CJ, Cruz AA, Eggleston PA, Lichtenstein LM, Togias AG: 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 89:1098–1110, 1992
Van Toorenenbergen AW, Van Wijk RG, Vermeulen AM, Zijlstra FJ: Increase of albumin, eosinophil cationic protein, histamine, leukotrienes and mast cell tryptase in nasal lavage fluid after challenge with inhalant allergen extract. Agents Actions 36 (Suppl C):C421-C424, 1992
Rasp G, Hochstrasser K: Tryptase in nasal fluid is a useful marker of allergic rhinitis. Allergy 48:72–74, 1993
Butrus SI, Ochsner KI, Abelson MB, Schwartz LB: The level of tryptase in human tears: An indicator of activation of conjunctival mast cells. Ophthalmology 97:1678–1683, 1990
Wenzel S, Irani AM, Sanders JM, Bradford TR, Schwartz LB: Immunoassay of tryptase from human mast cells. J Immunol Methods 86:139–142, 1986
Enander I, Matsson P, Nystrand J, Andersson A-S, Eklund E, Bradford TR, Schwartz LB: A new radioimmunoassay for human mast cell tryptase using monoclonal antibodies. J Immunol Methods 138:39–46, 1991
Schwartz LB: Monoclonal antibodies against human mast cell tryptase demonstrate shared antigenic sites on subunits of tryptase and selective localization of the enzyme to mast cells. J Immunol 134:526–531, 1985
Irani A-MA, Bradford TR, Kepley CL, Schechter NM, Schwartz LB: Detection of MCT and MCTC types of human mast cells by immunohistochemistry using new monoclonal anti-tryptase and anti-chymase antibodies. J Histochem Cytochem 37:1509–1515, 1989
Schwartz LB, Bradford TR, Lee DC, Chlebowski JF: Immunologic and physicochemical evidence for conformational changes occurring on conversion of human mast cell tryptase from active tetramer to inactive monomer: Production of monoclonal antibodies recognizing active tryptase. J Immunol 144:2304–2311, 1990
Schick B, Austen KF, Schwartz LB: Activation of rat serosal mast cells by chymase, an endogenous secretory granule protease. J Immunol 132:2571–2577, 1984
Schwartz LB, Bradford TR: Regulation of tryptase from human lung mast cells by heparin. Stabilization of the active tetramer. J Biol Chem 261:7372–7379, 1986
Craig SS, DeBlois G, Schwartz LB: Mast cells in human keloid, small intestine, and lung by an immunoperoxidase technique using a murine monoclonal antibody against tryptase. Am J Pathol 124:427–435, 1986
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 USA 83:4464–4468, 1986
Miller JS, Westin EH, Schwartz LB: Cloning and characterization of complementary DNA for human tryptase. J Clin Invest 84:1188–1195, 1989
Miller JS, Moxley G, Schwartz LB: Cloning and characterization of a second complementary DNA for human tryptase. J Clin Invest 86:864–870, 1990
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Schwartz, L.B., Bradford, T.R., Rouse, C. et al. Development of a new, more sensitive immunoassay for human tryptase: Use in systemic anaphylaxis. J Clin Immunol 14, 190–204 (1994). https://doi.org/10.1007/BF01533368
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DOI: https://doi.org/10.1007/BF01533368