Expression of Tissue Factor by Eosinophils in Patients with Chronic UrticariaCugno M.a · Marzano A.V.b · Tedeschi A.c · Fanoni D.b · Venegoni L.b · Asero R.d
aDepartment of Internal Medicine, bInstitute of Dermatological Sciences, cAllergy and Clinical Immunology Unit, IRCCS Foundation Maggiore Policlinico Hospital, Mangiagalli, Regina Elena and University of Milan, and dAmbulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano, Milan, Italy
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Background: Although several cases of chronic urticaria (CU) are currently regarded as autoimmune in origin, associated with histamine-releasing autoantibodies, an activation of blood coagulation via tissue factor (TF) and a strong expression of TF in lesional skin have been described. Eosinophils, which are involved in CU skin lesions, have recently been demonstrated as the major source of TF in human blood. We assessed whether eosinophils are the cellular source of TF in CU skin lesions. Methods: Twenty patients with severe CU were studied. Skin biopsy specimens were taken from wheals. The control group consisted of specimens of perilesional normal skin from different types of skin tumours (10) and various skin disorders with non-eosinophilic infiltrates, including leukocytoclastic vasculitis (7), lichen planus (8) and mastocytosis (3). TF expression was evaluated by immunohistochemical methods using an anti-TF monoclonal antibody. Co-localization of TF and eosinophil cationic protein, a classic cell marker of eosinophils, was investigated by double-staining studies using 2 specific monoclonal antibodies in the 4 specimens showing the highest TF reactivity scores. Results: All specimens from patients with CU clearly showed TF expression that was absent in all normal control specimens (p = 0.0001) and in the skin disorders with non-eosinophilic infiltrates (p = 0.001–0.0001). The double-staining experiments for TF and eosinophil cationic protein clearly showed that the TF-positive cells were eosinophils. Conclusions: Eosinophils are the main source of TF in CU lesional skin. This finding highlights the role of these cells in the pathophysiology of CU and might pave the way for new therapeutic strategies.
© 2008 S. Karger AG, Basel
- Grattan CEH, Francis DM, Hide M, Greaves MW: Detection of circulating histamine releasing autoantibodies with functional properties of anti IgE in chronic urticaria. Clin Exp Allergy 1991;21:695–704.
- Hide M, Francis DM, Grattan CEH, Hakimi J, Kochan JP, Greaves MW: Autoantibodies against the high-affinity IgE receptor as a cause of histamine release in chronic urticaria. N Engl J Med 1993;328:1599–1604.
- Tong LJ, Balakrishnan G, Kochan JP, Kinet JP, Kaplan AP: Assessment of autoimmunity in patients with chronic urticaria. J Allergy Clin Immunol 1997;99:461–465.
- Asero R, Tedeschi A, Lorini M, Salimbeni R, Zanoletti T, Miadonna A: Chronic urticaria: novel clinical and serological aspects. Clin Exp Allergy 2001;31:1105–1110.
- Sabroe RA, Grattan CE, Francis DM, Barr RM, Kobza Black A, Greaves MW: The autologous serum skin test: a screening test for autoantibodies in chronic idiopathic urticaria. Br J Dermatol 1999;140:446–452.
- Fagiolo U, Kricek F, Ruf C, Peserico A, Amadori A, Cancian M: Effects of complement inactivation and IgG depletion on skin reactivity to autologous serum in chronic idiopathic urticaria. J Allergy Clin Immunol 2000;106:567–572.
- Asero R, Tedeschi A, Riboldi P, Cugno M: Plasma of patients with chronic urticaria shows signs of thrombin generation, and its intradermal injection causes wheal-and-flare reactions much more frequently than autologous serum. J Allergy Clin Immunol 2006;117:1113–1117.
- Asero R, Tedeschi A, Coppola R, Griffini S, Paparella P, Riboldi P, Marzano AV, Fanoni D, Cugno M: Activation of the tissue pathway of blood coagulation in patients with chronic urticaria. J Allergy Clin Immunol 2007;119:705–710.
- Asero R, Tedeschi A, Riboldi P, Griffini S, Bonanni E, Cugno M: Severe chronic urticaria is associated with elevated plasma levels of D-dimer. Allergy 2008;63:176–180.
- Moosbauer C, Morgenstern E, Cuvelier SL, Manukyan D, Bidzhekov K, Albrecht S, Lohse P, Patel KD, Engelmann B: Eosinophils are a major intravascular location for tissue factor storage and exposure. Blood 2007;109:995–1002.
Kaplan AP: Urticaria and angioedema; in Adkinson NF, Yunginger YW, Busse WW, Bochner BS, Holgate ST, Simons FER (eds): Allergy: Principles and Practice, ed 6. Philadelphia, Mosby, 2003, pp 1537–1558.
- Sabroe RA, Poon E, Orchard GE, Lane D, Francis DM, Barr RM, Black MM, Black AK, Greaves MW: Cutaneous inflammatory cell infiltrate in chronic idiopathic urticaria: comparison of patients with and without anti-FcεRI or anti-IgE autoantibodies. J Allergy Clin Immunol 1999;103:484–493.
- Kambe N, Kitao A, Nishigori C, Miyachi Y: Late-phase urticaria: update. Curr Allergy Asthma Rep 2002;2:288–291.
- Byström J, Tenno T, Håkansson L, Amin K, Trulson A, Högbom E, Venge P: Monocytes, but not macrophages, produce the eosinophil cationic protein. APMIS 2001;109:507–516.
Schaeffer RC, Gong F, Bitrick MS, Smith TL: Thrombin and bradykinin initiate discrete endothelial solute permeability mechanisms. Am J Physiol 1993;264:1798–1809.
- Cirino G, Cicala C, Bucci MR, Sorrentino L, Maranganore JM, Stone SR: Thrombin functions as an inflammatory mediator through activation of its receptors. J Exp Med 1996;183:821–827.
- Nobe K, Sone T, Paul R J, Honda K. Trombin-induced force development in vascular endothelial cells: contribution to alteration of permeability mediated by calcium-dependent and -independent pathways. J Pharmacol Sci 2005;99:252–263.
- Razin E, Marx G. Thrombin-induced degranulation of cultured bone marrow-derived mast cells. J Immunol 1984;133:3282–3285.
- Vliagoftis H. Thrombin induces mast cell adhesion to fibronectin: evidence for the involvement of protease-activated receptor-1. J Immunol 2002;169:4551–4558.
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