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A New Image Analysis Method Based on Morphometric and Fractal Parameters for Rapid Evaluation of In Situ Mammalian Mast Cell Status

Published online by Cambridge University Press:  23 October 2015

Piper Wedman ,
Ahmed Aladhami ,
Mary Beste ,
Morgan K. Edwards ,
Alena Chumanevich ,
John W. Fuseler  and
Carole A. Oskeritzian
Piper Wedman
Affiliation:
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, South Carolina 29209, USA
Ahmed Aladhami
Affiliation:
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, South Carolina 29209, USA
Mary Beste
Affiliation:
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, South Carolina 29209, USA
Morgan K. Edwards
Affiliation:
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, South Carolina 29209, USA
Alena Chumanevich
Affiliation:
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, South Carolina 29209, USA
John W. Fuseler
Affiliation:
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, South Carolina 29209, USA
Carole A. Oskeritzian*
Affiliation:
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, South Carolina 29209, USA
*
*Corresponding author. Carole.Oskeritzian@uscmed.sc.edu
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Abstract

Apart from their effector functions in allergic disorders, tissue-resident mast cells (MC) are gaining recognition as initiators of inflammatory events through their distinctive ability to secrete many bioactive molecules harbored in cytoplasmic granules. Activation triggers mediator release through a regulated exocytosis named degranulation. MC activation is still substantiated by measuring systemic levels of MC-restricted mediators. However, identifying the anatomical location of MC activation is valuable for disease diagnosis. We designed a computer-assisted morphometric method based on image analysis of methylene blue (MB)-stained normal mouse skin tissue sections that quantitates actual in situ MC activation status. We reasoned MC cytoplasm could be viewed as an object featuring unique relative mass values based on activation status. Integrated optical density and area (A) ratios were significantly different between intact and degranulated MC (p<0.001). The examination of fractal characteristics is of translational diagnostic/prognostic value in cancer and readily applied to quantify cytoskeleton morphology and vasculature. Fractal dimension (D), a measure of their comparative space filling capacity and structural density, also differed significantly between intact and degranulated MC (p<0.001). Morphometric analysis provides a reliable and reproducible method for in situ quantification of MC activation status.

Keywords

mast cellsdegranulationfractal analysisin situmorphometry
Type
Equipment and Techniques Development
Information
Microscopy and Microanalysis , Volume 21 , Issue 6 , December 2015 , pp. 1573 - 1581
Copyright
© Microscopy Society of America 2015 

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Footnotes

†

These authors equally contributed to the study.

References

Akin, C., Valent, P. & Metcalfe, D.D. (2010). Mast cell activation syndrome: Proposed diagnostic criteria. J Allergy Clin Immunol 126, 1099–1104.CrossRefGoogle ScholarPubMed
Anderson, J.C., Babb, A.L. & Hlastala, M.P. (2005). A fractal analysis of the radial distribution of bronchial capillaries around large airways. J Appl Physiol 98, 850–855.Google Scholar
Aon, M.A., Roussel, M.R., Cortassa, S., O’Rourke, B., Murray, D.B., Beckmann, M. & Lloyd, D. (2008). The scale-free dynamics of eukaryotic cells. PLoS One 3, e3624.CrossRefGoogle ScholarPubMed
Arock, M., Schneider, E., Boissan, M., Tricottet, V. & Dy, M. (2002). Differentiation of human basophils: An overview of recent advances and pending questions. J Leuko Biol 71, 557–564.CrossRefGoogle ScholarPubMed
Brown, J.H., Gupta, V.K., Li, B.-L., Milne, B.T., Restrepo, C. & West, G.B. (2002). The fractal nature of nature: Power laws, ecological complexity and biodiversity. Phil Trans R Soc Lond B 357, 619–626.Google Scholar
Da Silva, E.Z.M., Jamur, M.C. & Oliver, C. (2014). Mast cell function: A new vision of an old cell. J Histochem Cytochem 62, 698–738.CrossRefGoogle ScholarPubMed
Di Ieva, A. (2012). Fractal analysis of microvascular networks in malignant brain tumors. Clin Neuropathol 31, 342–351.Google Scholar
Di Ieva, A., Grizzi, F., Ceva-Grimaldi, G., Russo, C., Gaetani, P., Aimar, E., Levi, D., Pisano, P., Tancioni, F., Nicola, G., Tschabitscher, M., Dioguardi, N. & Baena, R.R. (2007). Fractal dimension as a quantitator of the microvasculature of normal and adenomatous pituitary tissue. J Anat 211, 673–680.Google Scholar
Dioguardi, N., Grizzi, F., Franceschini, B., Bossi, P. & Russo, C. (2006). Liver fibrosis and tissue architectural change measurement using fractal-rectified metrics and Hurst’s exponent. World J Gastroenterol 12, 2187–2194.Google Scholar
Dioguardi, N., Grizzi, F., Fiamengo, B. & Russo, C. (2008). Metrically measuring liver biopsy: a chronic hepatitis B and C computer-aided morphologic description. World J Gastroenterol 14, 7335–7344.CrossRefGoogle Scholar
Doubal, F.N., MacGillivray, T.J., Patton, N., Dhillon, B., Dennis, M.S. & Wardlaw, J.M. (2010). Fractal analysis of retinal vessels suggests that a distinct vasculopathy causes lacunar stroke. Neurology 74, 1102–1107.Google Scholar
Ferro, D.P., Falconi, M.A., Adam, R.L., Ortega, M.M., Lima, C.P., De Souza, C.A., Lorand-Metze, I. & Metze, K. (2011). Fractal characteristics of May-Grünwald-Giemsa stained chromatin are independent prognostic factors for survival in multiple myeloma. PLoS One 6, e20706.Google Scholar
Fuseler, J.W., Bedenbaugh, A., Yekkala, K. & Baudino, T.A. (2010). Fractal and image analysis of the microvasculature in normal intestinal submucosa and intestinal polyps in Apc(Min/+) mice. Microsc Microanal 16, 73–79.Google Scholar
Fuseler, J.W., Merrill, D.M., Rogers, J.A., Grisham, M.B. & Wolf, R.E. (2006). Analysis and quantitation of NF-kappaB nuclear translocation in tumor necrosis factor alpha (TNF-alpha) activated vascular endothelial cells. Microsc Microanal 12, 269–276.Google Scholar
Fuseler, J.W., Millette, C.F., Davis, J.M. & Carver, W. (2007). Fractal and image analysis of morphological changes in the actin cytoskeleton of neonatal cardiac fibroblasts in response to mechanical stretch. Microsc Microanal 13, 133–143.Google Scholar
Fuseler, J.W. & Valarmathi, M.T. (2012). Modulation of the migration and differentiation potential of adult bone marrow stromal stem cells by nitric oxide. Biomaterials 33, 1032–1043.Google Scholar
Galli, S.J., Borregaard, N. & Wynn, T.A. (2011). Phenotypic and functional plasticity of cells of innate immunity: Macrophages, mast cells and neutrophils. Nat Immunol 12, 1035–1044.Google Scholar
Galli, S.J., Grimbaldeston, M. & Tsai, M. (2008). Immunomodulatory mast cells: Negative, as well as positive, regulators of immunity. Nat Rev Immunol 8, 478–486.Google Scholar
Galli, S.J. & Tsai, M. (2012). IgE and mast cells in allergic disease. Nat Immunol 18, 693–704.Google Scholar
Gerber, P.A., Buhren, B.A., Schrumpf, H., Homey, B., Zlotnik, A. & Hevezi, P. (2014). The top skin-associated genes: A comparative analysis of human and mouse skin transcriptomes. Biol Chem 395, 577–591.Google Scholar
Giannou, A.D., Marazioti, A., Spella, M., Kanellakis, N.I., Apostolopoulou, H., Psallidas, I., Prijovich, Z.M., Vreka, M., Zazara, D.E., Lilis, I., Papaleonidopoulos, V., Kairi, C.A., Patmanidi, A.L., Giopanou, I., Spiropoulou, N., Harokopos, V., Aidinis, V., Spyratos, D., Teliousi, S., Papadaki, H., Taraviras, S., Snyder, L.A., Eickelberg, O., Kardamakis, D., Iwakura, Y., Feyerabend, T.B., Rodewald, H.R., Kalomenidis, I., Blackwell, T.S., Agalioti, T. & Stathopoulos, G.T. (2015). Mast cells mediate malignant pleural effusion formation. J Clin Invest 125, 2317–2334.Google Scholar
Grizzi, F. & Dioguardi, N. (1999). A fractal scoring system for quantifying active collagen synthesis during chronic liver disease. Int J Chaos Theo Appl 21, 262–266.Google Scholar
Grizzi, F., Russo, C., Colombo, P., Franceschini, B., Frezza, E.E., Cobos, E. & Chiriva-Internati, M. (2005). Quantitative evaluation and modelling of two-dimensional neovascular network complexity: The surface fractal dimension. BMC Cancer 5, 14–23.Google Scholar
Hamilton, M.J., Hornick, J.L., Akin, C., Castells, M.C. & Greenberger, N.J. (2011). Mast cell activation syndrome: A newly recognized disorder with systemic clinical manifestations. J Allergy Clin Immunol 128, 147–152.Google Scholar
Hart, P.H., Grimbaldeston, M.A., Swift, G.J., Jaksic, A., Noonan, F.P. & Finlay-Jones, J.J. (1998). Dermal mast cells determine susceptibility to ultraviolet B-induced systemic suppression of contact hypersensitivity responses in mice. J Exp Med 187, 2045–2053.Google Scholar
Hart, P.H., Grimbaldeston, M.A., Hosszu, E.K., Swift, G.J., Noonan, F.P. & Finlay-Jones, J.J. (1999). Age-related changes in dermal mast cell prevalence in BALB/c mice: Functional importance and correlation with dermal mast cell expression of Kit. Immunology 98, 352–356.Google Scholar
Jelinek, H.F., Ristanovic, D. & Milosevic, N.T. (2011). The morphology and classification of α ganglion cells in the rat retinae: A fractal analysis study. J Neurosci Methods 201, 281–287.Google Scholar
Kalesnikoff, J. & Galli, S.J. (2008). New developments in mast cell biology. Nat Immunol 9, 1215–1223.Google Scholar
Lagunoff, D. (1974). Analysis of dye binding sites in mast cell granules. Biochemistry 19, 3982–3986.Google Scholar
Mandelbrot, B.B. (1982). The Fractal Geometry of Nature, 1st ed. New York: W. H. Freeman and Company.Google Scholar
Marshall, J.S. (2004). Mast-cell responses to pathogens. Nat Rev Immunol 4, 787–799.Google Scholar
Manera, M., Dezfuli, B.S., Borreca, C. & Giari, L. (2014). The use of fractal dimension and lacunarity in the characterization of mast cell degranulation in rainbow trout (Onchorhynchus mykiss). J Microsc 256, 82–89.Google Scholar
Mcnally, J.G. & Mazza, D. (2010). Fractal geometry in the nucleus. EMBO J 29, 2–3.Google Scholar
Moon, T.C., Befus, A.D. & Kulka, M. (2014). Mast cell mediators: Their differential release and the secretory pathways involved. Front Immunol 5, 1–18.Google Scholar
Moledina, S., de Bruyn, A., Schievano, S., Owens, C.M., Young, C., Haworth, S.G., Taylor, A.M., Schulze-Neick, I. & Muthurangu, V. (2011). Fractal branching quantifies vascular changes and predicts survival in pulmonary hypertension: a proof of principle study. Heart 97, 1245–1249.Google ScholarPubMed
Nezadal, M., Zemeskal, O. & Buchnicek, M. (2001). The box-counting: Critical study, 4th Conference on Prediction, Synergetic and More, The Faculty of Management, Institute of Information Technologies, Faculty of Technology, Tomas Bata University in Zlin, HarFA software, October 25–26, p. 18.Google Scholar
Oldford, S.A. & Marshall, J.S. (2015). Mast cells as targets for immunotherapy of solid tumors. Mol Immunol 63, 113–124.Google Scholar
Oskeritzian, C.A. (2015). Mast cell plasticity and sphingosine-1-phosphate in immunity, inflammation and cancer. Mol Immunol 63, 104–112.Google Scholar
Oskeritzian, C.A., Alvarez, S.E., Hait, N.C., Price, M.M., Milstien, S. & Spiegel, S. (2008). Distinct roles of sphingosine kinases 1 and 2 in human mast cell functions. Blood 111, 4193–4200.Google Scholar
Oskeritzian, C.A., Hait, N.C., Wedman, P., Chumanevich, A., Kolawole, E.M., Price, M.M., Falanga, Y.T., Harikumar, K.B., Ryan, J.J., Milstien, S., Sabbadini, R. & Speigel, S. (2015). The sphingosine-1-phosphate/sphingosine-1-phosphate receptor 2 axis regulates early airway T-cell infiltration in murine mast cell-dependent acute allergic responses. J Allergy Clin Immunol 135, 1008–1018.Google Scholar
Oskeritzian, C.A., Price, M.M., Ryan, J.J., Hait, N.C., Kapitonov, D., Falanga, Y., Morales, J.K., Milstien, S. & Spiegel, S. (2010). Essential role of sphingosine-1-phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema. J Exp Med 207, 465–474.Google Scholar
Qian, A.R., Li, D., Han, J., Gao, X., Di, S.M., Zhang, W., Hu, L.F. & Shang, P. (2012). Fractal dimension as a measure of altered actin cytoskeleton in MC3T3-E1 cells under simulated microgravity using 3-D/2-D clinostats. IEEE Trans Biomed Eng 59, 1374–1380.Google Scholar
Rafail, S., Kourtzelis, I., Foukas, P.G., Markiewski, M.M., Deangelis, R.A., Guariento, M., Ricklin, D., Grice, E.A. & Lambris, J.D. (2015). Complement deficiency promotes cutaneous wound healing in mice. J Immunol 194, 1285–1291.Google Scholar
Reber, L.L., Marichal, T. & Galli, S.J. (2012). New models for analyzing mast cell functions in vivo . Trends Immunol 33, 613–625.Google Scholar
Ribatti, D. (2013). Mast cells and macrophages exert beneficial and detrimental effects on tumor progression and angiogenesis. Immunol Lett 152, 83–88.Google Scholar
Rogers, J.A. & Fuseler, J.W. (2007). Regulation of NF-κB activation and nuclear translocation by exogenous nitric oxide (NO) donors in TNF-α activated vascular endothelial cells. Nitric Oxide 16, 379–391.CrossRefGoogle ScholarPubMed
Schwartz, L.B., Metcalfe, D.D., Miller, J.S., Earl, H. & Sullivan, T. (1987). Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis. N Engl J Med 316, 1622–1626.Google Scholar
Sedivy, R., Thurner, S., Budinsky, A.C., Kostler, W.J. & Zielinski, C.C. (2002). Short-term rhythmic proliferation of human breast cancer cell lines: Surface effects and fractal growth patterns. J Pathol 197, 163–169.CrossRefGoogle ScholarPubMed
Smith, T.G., Lange, G.D. & Marks, W.B. (1996). Fractal methods and results in cellular morphology-dimensions, lacunarity and multifractals. J Neurosci Methods 39, 123–136.CrossRefGoogle Scholar
Streba, L., Forţofoiu, M.C., Popa, C., Ciobanu, D., Gruia, C.L., Mogoanta, S.Ş. & Streba, C.T. (2015). A pilot study on the role of fractal analysis in the microscopic evaluation of colorectal cancers. Rom J Morphol Embryol 56, 191–196.Google Scholar
Thamrin, C., Stern, G. & Frey, U. (2010). Fractals for physicians. Paediatr Respir Rev 11, 123–131.Google Scholar
Theoharides, T.C., Alysandratos, K.-D., Angelidou, A., Delivanis, D.-A., Sismanopoulos, N., Zhang, B., Asadi, S., Vasiadi, M., Weng, Z., Miniati, A. & Kalogeromitros, D. (2012). Mast cells and inflammation. Biochim Biophys Acta 1822, 21–33.CrossRefGoogle ScholarPubMed
Valent, P., Horny, H.-P., Triggiani, M. & Arock, M. (2011). Clinical and laboratory parameters of mast cell activation as basis for the formulation of diagnostic criteria. Int Arch Allergy Immunol 156, 119–127.Google Scholar
Voehringer, D. (2013). Protective and pathological roles of mast cells and basophils. Nat Rev Immunol 13, 362–375.Google Scholar
Walter, R.J. Jr. & Berns, M.W. (1986). Digital image processing and analysis. In Video Microscopy, Inoue S. (Ed.), pp. 327–392. New York and London: Plenum Press.Google Scholar
Wernersson, S. & Pejler, G. (2014). Mast cell secretory granules: Armed for battle. Nat Rev Immunol 14, 478–494.Google Scholar
Wick, N., Thurner, S., Paiha, K., Sedivy, R., Vietor, I. & Huber, L.A. (2003). Quantitative measurement of cell migration using time-lapse videomicroscopy and non-linear system analysis. Histochem Cell Bio 119, 15–20.Google Scholar
Wolters, P.J., Mallen-St. Clair, J., Lewis, C.C., Villalta, S.A., Baluk, P., Erle, D.J. & Caughey, G.H. (2005). Tissue-selective mast cell reconstitution and differential lung gene expression in mast cell-deficient Kit W-sh /Kit W-sh sash mice. Clin Exp Allergy 35, 82–88.Google Scholar
Zhang, L., Liu, J.Z., Dean, D., Sahgal, V. & Yue, G.H. (2006). A three-dimensional fractal analysis method for quantifying white matter structure in human brain. J Neurosci Methods 150, 242–253.Google Scholar
Zouien, F.A., Kurdi, M., Booz, G.W. & Fuseler, J.W. (2014). Applying fractal dimension and image analysis to quantify fibrotic collagen deposition and organization in the normal and hypertensive heart. Microsc Microanal 20, 1134–1144.Google Scholar