Hostname: page-component-78c5997874-j824f Total loading time: 0 Render date: 2024-11-10T08:09:00.678Z Has data issue: false hasContentIssue false

Bee Venom Induced In Vivo Ultrastructural Reactions of Cells Involved in the Bone Marrow Erythropoiesis and of Circulating Red Blood Cells

Published online by Cambridge University Press:  04 February 2013

Adrian Florea*
Affiliation:
Department of Cell and Molecular Biology, “Iuliu Hațieganu”University of Medicine and Pharmacy, 6 Pasteur St., 400349, Cluj-Napoca, Romania
Constantin Crăciun
Affiliation:
Electron Microscopy Center, “Babeş-Bolyai” University, 5-7 Clinicilor St., 400006, Cluj-Napoca, Romania
*
*Corresponding author. E-mail: aflorea@umfcluj.ro; adrian_a_florea@yahoo.com
Get access

Abstract

Ultrastructural answer of bone marrow erythroid series and of red blood cells (RBCs) in Wistar rats to bee venom (BV) was analyzed by transmission and scanning electron microscopy, and corroborated with hematological data. A 5-day and a 30-day treatment with daily doses of 700 μg BV/kg and an acute-lethal treatment with a single dose of 62 mg BV/kg were performed. The 5-day treatment resulted in a reduced cellularity of the bone marrow, with necrosed proerythroblasts, polymorphous erythroblasts, and reticulocytes with cytoplasmic extensions, and a lower number of larger RBCs, with poikilocytosis (acanthocytosis) and anisocytosis, and reduced concentrations of hemoglobin. After the 30-day treatment, the bone marrow architecture was restored, but polymorphous erythroblasts and reticulocytes with thin extensions could still be observed, while the RBCs in higher number were smaller, many with abnormal shapes, especially acanthocytes. The acute treatment produced a partial depopulation of the bone marrow and ultrastructural changes of erythroblasts including abnormal mitochondrial cristae. The RBCs in lower number were bigger and crenated, with reduced concentrations of hemoglobin. Overall, BV was able to promote stress erythropoiesis in a time- and dose-related manner, mitochondrial cristae modification being a critical factor involved in the toxicity of the BV high doses.

Type
Biological Applications
Copyright
Copyright © Microscopy Society of America 2013

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bain, B.J. (1996). The bone marrow aspirate in healthy subjects. Br J Haematol 94, 206209.CrossRefGoogle ScholarPubMed
Bain, B.J. (2006). Blood Cells: A Practical Guide, 4th ed. Malden, MA: Blackwell Publishing, Inc. CrossRefGoogle Scholar
Bain, B.J. (2011). Blood cell morphology in health and disease. In Dacie and Lewis Practical Haematology, 11th ed., Bain, B.J., Bates, I., Laffan, M. & Lewis, S.M. (Eds.), pp. 70100. London: Elsevier Churchill Livingstone.Google Scholar
Bain, B.J., Clark, D.M., Lampert, I.A. & Wilkins, B.S. (2001). Bone Marrow Pathology, 3rd ed. Oxford: Blackwell Science Ltd. CrossRefGoogle Scholar
Barshishat-Kupper, M., Mungunsukh, O., Tipton, A.J., McCart, E.A., Panganiban, R.A.M., Davis, T.A., Landauer, M.R. & Day, R.M. (2011). Captopril modulates hypoxia-inducible factors and erythropoietin responses in a murine model of total body irradiation. Exp Hematol 39, 293304.CrossRefGoogle Scholar
Berg, O.G., Gelb, M.H., Tsai, M.D. & Jain, M.K. (2001). Interfacial enzymology: The secreted phospholipase A2-paradigm. Chem Rev 101, 26132653.CrossRefGoogle Scholar
Bessis, M. (1958). L'Ilot erythroblastique, unite fonctionelle de la moelle osseuse. Rev Hematol 13, 811.Google Scholar
Bessis, M. (1974). Corpuscles. An Atlas of Red Cell Shapes. New York: Springer-Verlag.Google Scholar
Bloom, W. & Fawcet, D.W. (1975). A Textbook of Histology. Philadelphia, PA: W.B. Saunders Co. Google Scholar
Boutin, A.T., Weidemann, A., Fu, Z., Mesropian, L., Gradin, K., Jamora, C., Wiesener, M., Eckardt, K.U., Koch, C.J., Ellies, L.G., Haddad, G., Haase, V.H., Simon, M.C., Poellinger, L., Powell, F.L. & Johnson, R.S. (2008). Epidermal sensing of oxygen is essential for systemic hypoxic response. Cell 133, 223234.CrossRefGoogle ScholarPubMed
Bresolin, N.L., Carvalho, F.L.C., Goes, J.E.C., Fernandes, V.R. & Barotto, A.M. (2002). Acute renal failure following massive attack by Africanized bee stings. Pediatr Nephrol 17, 625627.CrossRefGoogle ScholarPubMed
Burke, J.E. & Dennis, E.A. (2009). Phospholipase A2 structure/function, mechanism, and signaling. J Lipid Res 50, S237S242.CrossRefGoogle ScholarPubMed
Burkey, B.F., Hoffmann, P.K., Hassiepen, U., Trappe, J., Juedes, M. & Foley, J.E. (2008). Adverse effects of dipeptidyl peptidases 8 and 9 inhibition in rodents revisited. Diabetes Obes Metab 10, 10571061.CrossRefGoogle ScholarPubMed
Car, B.D. (2010). The hematopoietic system. In Schalm's Veterinary Hematology, 6th ed., Weiss, D.J. & Wardrop, K.J. (Eds.), pp. 2735. Ames, IA: Wiley-Blackwell.Google Scholar
Chasis, J.A. (2006). Erythrold system and its diseases. Erythroblastic islands: Specialized microenvironmental niches for erythropoiesis. Curr Opin Hematol 13, 137141.CrossRefGoogle Scholar
Chasis, J.A. & Mohandas, N. (2008). Erythroblastic islands: Niches for erythropoiesis. Blood 112, 470478.CrossRefGoogle ScholarPubMed
Cole, L.J. & Shipman, W.H. (1969). Chromatographic fractions of bee venom: Cytotoxicity for mouse bone marrow stem cells. Am J Physiol 217, 965968.CrossRefGoogle ScholarPubMed
Dempsey, C.E. (1990). The action of melittin on membranes. Biochim Biophys Acta 1031, 143161.CrossRefGoogle ScholarPubMed
Derelanko, M.J. & Hollinger, M.A. (1995). CRC Handbook of Toxicology. New York: CRC Press Inc. Google Scholar
Fitzgerald, K.T. & Flood, A.A. (2006). Hymenoptera stings. Clin Tech Small Anim Pract 21, 194204.CrossRefGoogle ScholarPubMed
Flachsenberger, W., Leigh, C.M. & Mirtschin, P.J. (1995). Sphero-echinocytosis of human red blood cells caused by snake, red-back spider, bee and blue-ringed octopus venoms and its inhibition by snake sera. Toxicon 33, 791797.CrossRefGoogle ScholarPubMed
Florea, A. & Crăciun, C. (2011). Abnormal mitochondrial cristae were experimentally generated by high doses of Apis mellifera venom in the rat adrenal cortex. Micron 42, 434442.CrossRefGoogle ScholarPubMed
Florea, A. & Crăciun, C. (2012). Bee (Apis mellifera) venom produced toxic effects of higher amplitude in rat thoracic aorta than in skeletal muscle—An ultrastructural study. Microsc Microanal 18, 304316.CrossRefGoogle ScholarPubMed
França, F.O.S., Benvenuti, L.A., Fan, H.W., Dos Santos, D.R., Hain, S.H., Picchi-Martins, F.R., Cardoso, J.L.C., Kamiguti, A.S., Theakston, R.D.G. & Warrell, D.A. (1994). Severe and fatal mass attacks by “killer” bees (Africanized honey bees—Apis mellifera scutellata) in Brazil: Clinicopathological studies with measurement of serum venom concentration. Q J Med 87, 269282.Google Scholar
Gad, S.C. & Chengelis, C.P. (1992). Animal Models in Toxicology. New York: Marcel Dekker Inc. Google Scholar
Ginsberg, N.J., Dauer, M. & Slotta, K.H. (1968). Melittin used as a protective agent against X-irradiation. Nature 220, 1334. CrossRefGoogle ScholarPubMed
Glättli, A., Chandrasekhar, I. & van Gunsteren, W.F. (2006). A molecular dynamics study of the bee venom melittin in aqueous solution, in methanol, and inserted in a phospholipid bilayer. Eur Biophys J 35, 255267.CrossRefGoogle Scholar
Goldstein, J., Newbury, D., Joy, D., Lyman, C., Echlin, P., Lifshin, E., Sawyer, L. & Michael, J. (2003). Scanning Electron Microscopy and X-Ray Microanalysis, 3rd ed. New York: Springer Publishing Co. CrossRefGoogle Scholar
Habermann, E. (1972). Bee and wasp venoms. The biochemistry and pharmacology of their peptides and enzymes are reviewed. Science 177, 314322.CrossRefGoogle Scholar
Habermann, E. & Neumann, W. (1957). Reinigung der phasphalipase A der bienegiftes. Biochem Z 328, 465473.Google Scholar
Hebbel, R.P. & Miller, W.J. (1984). Phagocytosis of sickle erythrocytes: Immunologic and oxidative determinants of hemolytic anemia. Blood 64, 733741.CrossRefGoogle ScholarPubMed
Heynen, M.J. & Verwilghen, R.L. (1982). A quantitative ultrastructural study of normal rat erythroblasts and reticulocytes. Cell Tissue Res 224, 397408.CrossRefGoogle ScholarPubMed
Hodges, V.M., Rainey, S., Lappin, T.R. & Maxwell, A.P. (2007). Pathophysiology of anemia and erythrocytosis. Crit Rev Oncol Hematol 64, 139158.CrossRefGoogle ScholarPubMed
Hristova, K., Dempsey, C.E. & White, S.H. (2001). Structure, location, and lipid perturbations of melittin at the membrane interface. Biophys J 80, 801811.CrossRefGoogle ScholarPubMed
Hui, S.W., Stewart, C.M. & Cherry, R.J. (1990). Electron microscopic observation of the aggregation of membrane proteins in human erythrocyte by melittin. Biochim Biophys Acta 1023, 335340.CrossRefGoogle ScholarPubMed
Iliev, Y.T., Tufkova, S.G. & Prancheva, M.G. (2010). A rare case of severe intoxication from multiple bee stings with afavorable outcome. Folia Medica 52, 7477.CrossRefGoogle Scholar
Killion, J.J. & Dunn, J.D. (1986). Differential cytolysis of murine spleen, bone-marrow, and leukemia cells by melittin reveals differences in membrane topography. Biochem Biophys Res Commun 139, 222227.CrossRefGoogle ScholarPubMed
Kolecki, P. (1999). Delayed toxic reaction following massive bee envenomation. Ann Emerg Med 33, 114116.CrossRefGoogle ScholarPubMed
Koszalka, M.F. (1949). Multiple bee stings with hemoglobinuria and recovery: Report of a case. Bull US Army Med Depart 9, 212217.Google ScholarPubMed
Koury, M.J. (2005). Erythropoietin: The story of hypoxia and a finely regulated hematopoietic hormone. Exp Hematol 33, 12631270.CrossRefGoogle Scholar
Krylov, V.N., Koryagin, A.S. & Erofeeva, E.A. (2008). Comparative analysis of radioprotective properties of some zootoxins. J Evol Biochem Phys 44, 501506.CrossRefGoogle ScholarPubMed
Lee, H.S., Chung, S.H., Song, M.Y., Kim, S.S., Shin, H.D, Shim, W.J., Han, A.R. & Lee, J.S. (2008). Effects of bee venom on the maturation of murine dendritic cells stimulated by LPS. J Ethnopharmacol 120, 215219.CrossRefGoogle ScholarPubMed
Murphy, M.J. Jr., Bertles, J.F. & Gordon, A.S. (1971). Identifying characteristics of the haematopoietic precursor cell. J Cell Sci 9, 2347.CrossRefGoogle ScholarPubMed
Neumann, W., Habermann, E. & Amend, G. (1952). Zur papierelektrophoresis den fraktionierung tierischer gifte. Naturwissenschaften 39, 286287.CrossRefGoogle Scholar
Oliver, C.S. (2010). Erythropoiesis. In Schalm's Veterinary Hematology, 6th ed., Weiss, D.J. & Wardrop, K.J. (Eds.), pp. 3642. Ames, IA: Wiley-Blackwell.Google Scholar
Orlic, D., Gordon, A.S. & Rhodin, J.A.G. (1968). Ultrastructural and autoradiographic studies of erythropoietin-induced red cell production. Ann NY Acad Sci 149, 198216.CrossRefGoogle ScholarPubMed
Pierre, R.V. (2002). Red cell morphology and the peripheral blood film. Clin Lab Med 22, 2561.CrossRefGoogle ScholarPubMed
Pulido-Méndez, M., Rodriguez-Acosta, A. & Finol, H.J. (2002). Adrenal cortex ultrastructural alterations caused by zootoxins. Microsc Microanal 8(Suppl 2), 926CD927CD.CrossRefGoogle Scholar
Rogers, H.M., Yu, X., Wen, J., Smith, R., Fibach, E. & Noguchi, C.T. (2008). Hypoxia alters progression of the erythroid program. Exp Hematol 36, 1727.CrossRefGoogle ScholarPubMed
Roque, M., D'Anna, C., Gatti, C. & Veuthey, T. (2008). Hematological and morphological analysis of the erythropoietic regenerative response in phenylhydrazine-induced hemolytic anemia in mice. Scand J Lab Anim Sci 35, 181190.Google Scholar
Rosenfeld, G. (1976). Human envenomation by bee stings. In Toxins: Animal, Plant and Microbial, Rosenberg, P. (Ed.), pp. 692693. Oxford, UK: Pergamon Press.Google Scholar
Schwartz, R.S., Tanaka, Y., Fidler, I.J., Chiu, D.T.Y., Lubin, B. & Schroit, A.J. (1985). Increased adherence of sickled and phosphatidylserine-elriched human erythrocytes to cultured human peripheral blood monocytes. J Clin Invest 75, 19651972.CrossRefGoogle ScholarPubMed
Sharkey, L.C. & Hill, S.A. (2010). Structure of bone marrow. In Schalm's Veterinary Hematology, 6th ed., Weiss, D.J. & Wardrop, K.J. (Eds.), pp. 813. Ames, IA: Wiley-Blackwell.Google Scholar
Shipolini, R.A., Callewaert, G.L., Cottrell, R.C., Doonan, S., Vernan, C.A. & Banks, B.E.C. (1971). Phospholipase A from bee venom. Eur J Biochem 20, 459468.CrossRefGoogle ScholarPubMed
Terwilliger, T.C., Weissman, L. & Eisenberg, D. (1981). The structure of melittin in the form I crystals and its implication for melittin's lytic and surface activities. Biophys J 37, 353361.CrossRefGoogle Scholar
Theml, H., Diem, H. & Haferlach, T. (2004). Color Atlas of Hematology—Practical Microscopic and Clinical Diagnosis, 2nd ed. Stuttgart, Germany: Georg Thieme Verlag.CrossRefGoogle Scholar
Tosteson, M.T., Holmes, S.J., Razin, M. & Tosteson, D.C. (1985). Melittin lysis of red cells. J Membr Biol 87, 3544.CrossRefGoogle ScholarPubMed
Tu, A.T. (1977). Venoms: Chemistry and Molecular Biology. New York: Wiley Interscience.Google Scholar
Varanda, E.A., Takahashi, C.S., Soares, A.E.E. & Barreto, S.A.J. (1992). Effect of Apis mellifera bee venom and gamma radiation on bone marrow cells of Wistar rats treated in vivo . Rev Brasil Genet 15, 807819.Google Scholar
Varanda, E.A. & Tavares, D.C. (1998). Radioprotection: Mechanisms and radioprotective agents including honeybee venom. J Venom Anim Toxins 4, 521.CrossRefGoogle Scholar
Watt, I.M. (2003). The Principles and Practice of Electron Microscopy. Cambridge, UK: Cambridge University Press.Google Scholar
Wickramasinghe, S.N. (2007). Bone Marrow . In Histology for Pathologists, 3rd ed., Mills, S.E. & Stenberg, S. (Eds.), pp. 800836. Philadelphia, PA: Lippincott Williams & Wilkins.Google Scholar
Wilson, J.G. & Tavassoli, M. (1994). Microenvironmental factors involved in the establishment of erythropoiesis in bone marrow. Ann NY Acad Sci 718, 271284.CrossRefGoogle ScholarPubMed
Zalat, S., Nabil, Z., Hussein, A. & Rakha, M. (1999). Biochemical and haematological studies of some solitary and social bee venoms. Egypt J Biol 1, 5771.Google Scholar