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International Journal of Legal Medicine
Published in: International Journal of Legal Medicine 1/2016

01-01-2016 | Original Article

Are mast cells implicated in asphyxia?

Authors: Barbara Muciaccia, Cristina Sestili, Stefania De Grossi, Annarita Vestri, Luigi Cipolloni, Rossana Cecchi

Published in: International Journal of Legal Medicine | Issue 1/2016

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Abstract

In a previous immunohistochemical (IHC) study, we documented the reaction of lung tissue vessels to hypoxia through the immunodetection of HIF1-α protein, a key regulator of cellular response to hypoxic conditions. Findings showing that asphyxia deaths are associated with an increase in the number of mast cell (MC)-derived tryptase enzymes in the blood suggests that HIF1-α production may be correlated with MC activation in hypoxic conditions. This hypothesis prompted us to investigate the possible role of pulmonary MC in acute asphyxia deaths. Lung of 47 medico-legal autopsy cases (35 asphyxia/hypoxia deaths, 11 controls, and 1 anaphylactic death) were processed by IHC analysis using anti-CD117 (c-Kit) antibody to investigate peri-airway and peri-vascular MC together with their counts and features. Results showed a significant increase in peri-vascular c-kit+ MC in some asphyxia deaths, such as hanging, strangulation, and aspiration deaths. A strong activation of MC in peri-airway and peri-vascular areas was also observed in lung samples from the anaphylaxis case, which was used as a positive control. Our study points to the potential role of MC in hypoxia and suggests that an evaluation of MC in the lungs may be a useful parameter when forensic pathologists are required to make a differential diagnosis between acute asphyxia deaths and other kinds of death.
Literature
1.
Cecchi R, Sestili, Prosperini G, Cecchetto G, Vicini E, Viel G, Muciaccia B (2014) Markers of mechanical asphyxia: immunohistochemical study on autoptic lung tissues. Int J Legal Med 128(1):117–125PubMedCrossRef
2.
Edston E, Eriksson O, van Hage M (2007) Mast cell tryptase in postmortem serum-reference values and confounders. Int J Legal Med 121(4):275–280PubMedCrossRef
3.
4.
Norrby K, Jakobsson A, Sörbo J (1986) Mast-cell-mediated angiogenesis: a novel experimental model using the rat mesentery. Virchows Arch B Cell Pathol Incl Mol Pathol 52(3):195–206PubMedCrossRef
5.
Maltby S, Khazaie K, McNagny KM (2009) Mast-cells in Tumor Growth: Angiogenesis, Tissue Remodeling and Immune-modulation. Biochim Biophys Acta 1796(1):19–26PubMedPubMedCentral
6.
Taylor ML, Metcalfe DD (2001) Mast-cells in allergy and host defense. Allergy Asthma Proc 22(3):115–119PubMedCrossRef
7.
Koshino T, Arai Y, Miyamoto Y, Sano Y, Itami M, Teshima S, Hirai K, Takaishi T, Ito K, Morita Y (1996) Airway basophil and mast cell density in patients with bronchial asthma: relationship to bronchial hyperresponsiveness. J Asthma 33(2):89–95PubMedCrossRef
8.
Anand P, Singh B, Jaggi AS, Singh N (2012) Mast-cells: an expanding pathophysiological role from allergy to other disorders. Naunyn Schmiedeberg's Arch Pharmacol 385:657–670CrossRef
9.
Mican JM, Metcalfe DD (1990) Arthritis and mast cell activation. J Allergy Clin Immunol 86:677–683PubMedCrossRef
10.
11.
Yano H, Kinuta M, Tateishi H, Nakano Y, Matsui S, Monden T, Okamura J, Sakai M, Okamoto S (1999) Mast cell infiltration around gastric cancer cells correlates with tumor angiogenesis and metastasis. Gastric Cancer 2(1):26–32PubMedCrossRef
12.
Steiner DR, Gonzalez NC, Wood JG (2003) Mast-cells mediate the microvascular inflammatory response to systemic hypoxia. J Appl Physiol 94(1):325–334PubMedCrossRef
13.
Metz M, Grimbaldeston MA, Nakae S, Piliponsky AM, Tsai M, Galli SJ (2007) Mast-cells in the promotion and limitation of chronic inflammation. Immunol Rev 217:304–328PubMedCrossRef
14.
Herget J, Ježek V (1989) Pulmonary hypertension in chronic lung disease. In: Ca W (ed) Pulmonary hypertension problems and controversies. Denolin H. Elsevier Publ Co, Amsterdam, pp 142–162
15.
16.
Maxová H, Herget J, Vízek M (2012) Lung mast-cells and hypoxic pulmonary hypertension. Physiol Res Mar 61(1):1–11
17.
Karakiulakis G, Papakonstantinou E, Aletras AJ, Tamm M, Roth M (2007) Cell type-specific effect of hypoxia and platelet-derived growth factor-BB on extracellular matrix turnover and its consequences for lung remodeling. J Biol Chem 282:908–915PubMedCrossRef
18.
Levick SP, Melendez GC, Plante E, Mclarty JL, Brower GL, Janicki JS (2011) Cardiac mast-cells: the centrepiece in adverse myocardial remodelling. Cardiovasc Res 89(1):12–19PubMedCrossRef
19.
Franceschini B, Ceva-Grimaldi G, Russo C, Dioguardi N, Grizzi F (2006) The complex functions of MASTCELLS in chronic human liver diseases. Dig Dis Sci 51(12):2248–2256PubMedCrossRef
20.
Esposito I, Friess H, Kappeler A, Shrikhande S, Kleeff J, Ramesh H, Zimmermann A, Buchler MW (2001) Mast cell distribution and activation in chronic pancreatitis. Hum Pathol 32(11):1174–1183PubMedCrossRef
21.
Banasova A, Maxova H, Hampl V, Vizek M, Povysilova V, Novotna J, Vajnerova O, Hnilickova O, Herget J (2008) Prevention of mast cell degranulation by disodium cromoglycate attenuates the development of hypoxic pulmonary hypertension in rats exposed to chronic hypoxia. Respiration 76(1):102–107PubMedCrossRef
22.
Nadziejko CE, Loud AV, Kikkawa Y (1989) Effect of alveolar hypoxia on pulmonary mast-cells in vivo. Am Rev Respir Dis 140(3):743–748PubMedCrossRef
23.
Migally NB, Tucker A, Greenlees K, Wright M, Zambernard J (1983) Density and ultrastructure of mast-cells in lung vessels of aging rats exposed to and recovering from chronic hypoxia. Cell Tissue Res 232(3):601–608PubMedCrossRef
24.
Kay JM, Waymire JC, Grover RF (1974) Lung mast cell hyperplasia and pulmonary histamine-forming capacity in hypoxic rats. Am J Physiol 226(1):178–184PubMedCrossRef
25.
Tucker A, Mc Murtry I, Alexander AF, Reeves JT, Grover RF (1977) Lung mast cell density and distribution in chronically hypoxic animals. J Appl Physiol 42(2):174–178PubMedCrossRef
26.
Nakanishi I, Tajima F, Nakamura A, Yagura SY, Ookawara T, Yamashita H, Suzuki K, Taniguchi N, Ohno H (1995) Effects of hypobaric hypoxia on antioxidant enzymes in rats. J Physiol 489(Pt 3):869–876PubMedPubMedCentralCrossRef
27.
Hampl V, Herget J (2000) Role of nitric oxide in the pathogenesis of chronic pulmonary hypertension. Physiol Rev 80(4):1337–1372PubMedCrossRef
28.
Lachmanova V, Hnilickova O, Povysilova V, Hampl V, Herget J (2005) N-acetylcysteine inhibits hypoxic pulmonary hypertension most effectively in the initial phase of chronic hypoxia. Life Sci 77(2):175–182PubMedCrossRef
29.
Vajner L, Vytasek R, Lachmanova V, Uhlik J, Konradova V, Novotna J, Hampl V, Herget J (2006) Acute and chronic hypoxia as well as 7-day recovery from chronic hypoxia affects the distribution of pulmonary mast-cells and their MMP-13 expression in rats. Int J Exp Pathol 87(5):383–391PubMedPubMedCentralCrossRef
30.
Fineschi V, Cecchi R, Centini F, Pagliacci Reattelli L, Turillazzi E (2001) Immunohistochemical quantification of pulmonary mast cell and post mortem blood dosage of tryptase and eosinophil cationic protein in 48 heroin- related deaths. Forensic Sci Int 120:189–194PubMedCrossRef
31.
Arber DA, Tamayo R, Weiss LM (1998) Paraffin section detection of the c-kit gene product (CD117) in human tissues: value in the diagnosis of mast cell disorders. Hum Pathol 29(5):498–504PubMedCrossRef
32.
Fukuda T, Kamishima T, Tsuura Y, Suzuki T, Kakihara T, Naito M, Kishi K, Matsumoto K, Shibata A, Seito T (1995) Expression of the c-kit gene product in normal and neoplastic mast-cells but not in neoplastic basophil/mast cell precursors from chronic myelogenous leukaemia. J Pathol 177(2):139–146PubMedCrossRef
33.
Muciaccia B, Sette C, Paronetto MP, Barchi M, Pensini S, D’Agostino A, Gandini L, Geremia R, Stefanini M, Rossi P (2010) Expression of a truncated form of KIT tyrosine kinase in human spermatozoa correlates with sperm DNA integrity. Hum Reprod 25:2188–2202PubMedCrossRef
34.
Lennartsson J, Rönnstrand L (2012) Stem cell factor receptor/c-Kit: from basic science to clinical implications. Physiol Rev 92(4):1619–1649PubMedCrossRef
35.
Gambaryan N, Perros F, Montani D, Cohen-Kaminsky S, Mazmanian GM, Humbert M (2010) Imatinib inhibits bone marrow-derived c-kit + cell mobilisation in hypoxic pulmonary hypertension. Eur Respir J 36(5):1209–1211PubMedCrossRef
36.
Gambaryan N, Perros F, Montani D, Cohen-Kaminsky S, Mazmanian M, Renaud JF, Simonneau G, Lombet A, Humbert M (2011) Targeting of c-kit + haematopoietic progenitor cells prevents hypoxic pulmonary hypertension. Eur Respir J 37(6):1392–1399PubMedCrossRef
37.
Ferranti F, Muciaccia B, Ricci G, Dovere L, Canipari R, Magliocca F, Stefanini M, Catizone A, Vicini E (2012) Glial cell line-derived neurotrophic factor promotes invasive behaviour in testicular seminoma cells. Int J Androl 35:758–768PubMedCrossRef
38.
Hunt LW, Colby TV, Weiler DA, Sur S, Butterfield JH (1992) Immunofluorescent staining for MASTCELLS in idiopathic pulmonary fibrosis: quantification and evidence for extracellular release of mast cell tryptase. Mayo Clin Proc 67(10):941–948PubMedCrossRef
39.
Hawkins RA, Claman HN, Clark RA, Steigerwald JC (1985) Increased dermal mast cell populations in progressive systemic sclerosis: a link in chronic fibrosis. Ann Intern Med 102(2):182–186PubMedCrossRef
40.
Cha SI, Chang CS, Kim EK, Lee JW, Matthay MA, Golden JA, Elicker BM, Jones K, Collard HR, Wolters PJ (2012) Lung mast cell density defines a subpopulation of patients with idiopathic pulmonary fibrosis. Histopathology 61:98–106PubMedPubMedCentralCrossRef
41.
Van der Veer WM, Bloemen MC, Ulrich MM, Molema G, Van Zuijlen PP, Middelkoop E, Niessen FB (2009) Potential cellular and molecular causes of hypertrophic scar formation. Burns 35:15–29PubMedCrossRef
42.
Inoue Y, King TE Jr, Tinkle SS, Dockstader K, Newman LS (1996) Human mast cell basic fibroblast growth factor in pulmonary fibrotic disorders. Am J Pathol 149:2037–2054PubMedPubMedCentral
43.
Corallini S, Fera S, Grisanti L, Falciatori I, Muciaccia B, Stefanini M, Vicini E (2006) Expression of the adaptor protein m-Numb in mouse male germ cells. Reproduction 132:887–897PubMedCrossRef
44.
Du Chesne A, Cecchi R, Püschel K, Brinkmann B (1996) Macrophage subtype patterns in protracted asphyxiation. Int J Legal Med 109:163–166PubMedCrossRef
45.
Betz P, Nerlich A, Penning R, Eisenmenger W (1993) Alveolar macrophages and the diagnosis of drowning. Forensic Sci Int 63:217–224CrossRef
46.
Betz P, Beier G, Eisenmenger XW (1994) Pulmonary giant cells and traumatic asphyxia. Int J Legal Med 106:258–261PubMedCrossRef
47.
Vacchiano G, D'Armiento F, Torino R (2001) Is the appearance of macrophages in pulmonary tissue related to time of asphyxia? Forensic Sci Int 115:9–14PubMedCrossRef
48.
Vacchiano G (2002) Letter to the Editor. Role of pulmonary macrophages and giant cells in fatal asphyxia. Forensic Sci Int 127:245CrossRef
49.
Wilcox JN, Okamoto EI, Nakahara KI, Vinten-Johansen J (2001) Perivascular responses after angioplasty which may contribute to postangioplasty restenosis: a role for circulating myofibroblast precursors? Ann NY Acad Sci 947:68–90PubMedCrossRef
50.
Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH, Verfaillie CM (2002) Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest 109(3):337–346PubMedPubMedCentralCrossRef
51.
Angelini DJ, Su Q, Kolosova IA, Fan C, Skinner JT, Yamaji-Kegan K, Collector M, Sharkis SJ, Johns RA (2010) Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMa) recruits bone marrow-derived cells to the murine pulmonary vasculature. PLoS ONE 5(6):e11251PubMedPubMedCentralCrossRef
52.
Montani D, Perros F, Gambaryan N, Girerd B, Dorfmuller P, Price LC, Huertas A, Hammad H, Lambrecht B, Simonneau G, Launay JM, Cohen-Kaminsky S, Humbert M (2011) C-kit-positive cells accumulate in remodeled vessels of idiopathic pulmonary arterial hypertension. Am J Respir Crit Med 184(1):116–123CrossRef
53.
Dahlin JS, Hallgren J (2015) Mast cell progenitors: origin, development and migration to tissue. Mol Immunol 63:9–17PubMedCrossRef
54.
55.
Hallgren J, Jones TG, Abonia JP, Xing W, Humbles A, Austen KF, Gurish MF (2007) Pulmonary CXCR2 regulates VCAM-1 and antigen-induced recruitment of mast cell progenitors. Proc Natl Acad Sci USA 104(51):20478–20483PubMedPubMedCentralCrossRef
56.
Chao J, Donham P, Van Rooijen N, Wood JG, Gonzalez NC (2011) Monocyte chemoattractant protein-1 released from alveolar macrophages mediates the systemic inflammation of acute alveolar hypoxia. Am J Respir Cell Mol Biol 45(1):53–61PubMedCrossRef
57.
Walczak-Drzewiecka A, Ratajewski M, Wagner W, Dastych J (2008) HIF-1alpha is up-regulated in activated mast-cells by a process that involves calcineurin and NFAT. J Immunol 181(3):1665–1672PubMedCrossRef
58.
Reszec J, Hermanowicz A, Rutkowski R, Bernaczyk P, Mariak Z, Chyczewski L (2013) Evaluation of mast cells and hypoxia inducible factor-1 expression in meningiomas of various grades in correlation with peritumoral brain edema. J Neuro-Oncol 115(1):119–125CrossRef
59.
Jeong HJ, Oh HA, Nam SY, Han NR, Kim YS, Kim JH, Lee SJ, Kim MH, Moon PD, Kim HM, Oh HA (2013) The critical role of mast cell-derived hypoxia-inducible factor-1α in human and mice melanoma growth. Int J Cancer 132(11):2492–2501PubMedCrossRef
60.
Metadata
Title
Are mast cells implicated in asphyxia?
Authors
Barbara Muciaccia
Cristina Sestili
Stefania De Grossi
Annarita Vestri
Luigi Cipolloni
Rossana Cecchi
Publication date
01-01-2016
Publisher
Springer Berlin Heidelberg
Published in
International Journal of Legal Medicine / Issue 1/2016
Print ISSN: 0937-9827
Electronic ISSN: 1437-1596
DOI
https://doi.org/10.1007/s00414-015-1211-5

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