Immunologic Research

, Volume 66, Issue 2, pp 271–280 | Cite as

Phagocytosis and oxycytosis: two arms of human innate immunity

  • Hayk Minasyan
Original Article
First Online:
  • 78 Downloads

Abstract

Human innate immunity operates in two compartments: extravascular (the tissues) and intravascular (the bloodstream). Physical conditions (fluid dynamics) in the compartments are different and, as a result, bactericidal mechanisms and involved cells are different as well. In relatively static media (the tissues, lymph nodes), bacteria are killed by phagocytes; in dynamic media (the bloodstream), bacteria are killed by erythrocytes. In the tissues and lymph nodes, resident macrophages and transmigrated from blood leukocytes (neutrophils and monocytes) recognize, engulf, kill, and digest bacteria; the clearance of the bloodstream from bacteria is performed by oxycytosis: erythrocytes catch bacteria by electric charge attraction and kill them by the oxygen released from oxyhemoglobin. Killed by erythrocytes, bacteria are decomposed and digested in the liver and the spleen. Phagocytosis by leukocytes in the tissues and oxycytosis by erythrocytes in the bloodstream are the main bactericidal mechanisms of human innate immunity.

Keywords

Innate immunity Bacteremia Phagocytosis Oxycytosis 
This is a preview of subscription content, log in to check access

Notes

Compliance with ethical standards

Conflict of interest

The author declares that he has no conflict of interest.

References

  1. 1.
    Metchnikoff E. Sur la lutte des cellules de l’organisme contre l’invasion des microbes. Ann Inst Pasteur. 1887;1:321.Google Scholar
  2. 2.
    Metchnikoff E. Lecture on phagocytosis and immunity. BMJ. 1891;1:213–7.Google Scholar
  3. 3.
    Metchnikoff E. Über die phagocytäre Rolle der Tuberkelriesenzellen. (about the phagocytic role of the large tubercle cells). Virchows Archiv (Virchow’s Archive). 1888;113:63–94.Google Scholar
  4. 4.
    Lange B, Gutdeutsch H. Experimentelle Untersuchungen uber die Organdisposition und uber die Immunität nach Infektionen ohne nachweisbare Erkrankung. Z Hyg Infekt. 1928;109:253–65.Google Scholar
  5. 5.
    Dutton AAC. The influence of the route of infection on lethal infections in mice. Brit J Exptl Pathol. 1955;36:128–36.Google Scholar
  6. 6.
    Rogers D. Host mechanisms which act to remove bacteria from the bloodstream. Microbiol Mol Biol Rev. 1960;24(1):50–66.Google Scholar
  7. 7.
    Wright HD. Experimental pneumococcal septicaemia and anti-pneumococcal immunity. J Pathol Bacteriol. 1927;30:185–252.Google Scholar
  8. 8.
    Smith JM, DuBos RJ. The effect of nutritional disturbances on the susceptibility of mice to staphylococcal infections. J Exptl Med. 1956;103:109–18.Google Scholar
  9. 9.
    Gordon LE, Cooper DB, Miller CP. Clearance of bacteria from the blood of irradiated rabbits. Proc Soc Exptl Biol Med. 1955;89:577–9.Google Scholar
  10. 10.
    Callaway JL, Kerby G. Splanchnic removal of bacteria from the circulating blood of irradiated rabbits. Arch Dermatol Syphilol. 1951;63:200–6.Google Scholar
  11. 11.
    Rogers DE. Studies on bacteriemia. I. Mechanisms relating to the persistence of bacteriemia in rabbits following the intravenous injection of staphylococci. J Exptl Med. 1956;103:713–42.Google Scholar
  12. 12.
    Rogers DE, Melly MA. Studies on bacteriemia. II. Further observations on the granulocytopenia induced by the intravenous injection of staphylococci. J Exptl Med. 1957;106:99–112.Google Scholar
  13. 13.
    Martin SP, Kerby GP. Effect of adrenal hormone overdosage on bacterial removal by the splanchnic viscera. Proc Soc Exptl Biol Med. 1952;81:73–5.Google Scholar
  14. 14.
    Fine J. Relation of bacteria to the failure of blood-volume therapy in traumatic shock. New Engl J Med. 1954;250:889–5.PubMedGoogle Scholar
  15. 15.
    Balch HH, Evans JR. The influence of acute renal failure on resistance to infection: an experimental study. Ann Surg. 1956;144:191–7.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Reichel HA. Removal of bacteria from the blood stream: experiments tending to determine the rate of removal of injected bacteria in the blood. Proc Staff Meet Mayo Clin. 1939;14:138–43.Google Scholar
  17. 17.
    Martin SP, Kerby GP. The spanchnic removal in rabbits during fatal bacteriemias of circulating organisms and of superimposed non pathogenic bacteria. J Exptl Med. 1950;92:45–9.Google Scholar
  18. 18.
    Bull CG, McKee CM. The relation of blood platelets to the in vivo agglutination of bacteria and their disappearance from the blood stream. Am J Hyg. 1922;2:208–24.Google Scholar
  19. 19.
    Govaerts P. Action du serum antiplaquettique sur l'6limination des microbes introduits dans la circulation. Compt Rend Soc Biol. 1921;85:667–78.Google Scholar
  20. 20.
    Berlin JA, Abrutyn E, Strom BL, Kinman JL, Levison ME, Korzeniowski OM, et al. Incidence of infective endocarditis in the Delaware Valley, 1988-1990. Am J Cardiol. 1995;76:933–6.PubMedGoogle Scholar
  21. 21.
    Sande MA, Lee BL, Mills J. Endocarditis in intravenous drug users. In: Kaye D, editor. Infective endocarditis. New York City: Raven Press; 1992. p. 345.Google Scholar
  22. 22.
    Weinstein WL, Brusch JL. Infective endocarditis. New York City: Oxford University Press; 1996.Google Scholar
  23. 23.
    Spijkerman IJ, van Ameijden EJ, Mientjes GH, et al. Human immunodeficiency virus infection and other risk factors for skin abscesses and endocarditis among injection drug users. J Clin Epidemiol. 1996;49:1149–54.PubMedGoogle Scholar
  24. 24.
    Olsson CRA, Romansky MJ. Staphylococcal tricuspid endocarditis in heroin addicts. Ann Intern Med. 1962;57(5):755–62.PubMedGoogle Scholar
  25. 25.
    Levine DP, Crane LR, Zervos MJ. Bacteremia in narcotic addicts at the Detroit Medical Center. II. Infectious endocarditis: a prospective comparative study. Rev Infect Dis. 1986;8(3):374–96.PubMedGoogle Scholar
  26. 26.
    Gardner EM, Kestler M, Bieler A, Belknap RW. Clostridium butyricum sepsis in an injection drug user with an indwelling central venous catheter. J Med Microbiol. 2008;57(2):236–9.PubMedGoogle Scholar
  27. 27.
    Rieg S, Bauer TM, Peyerl-Hoffmann G, Held H, Ritter W, Wagner D, et al. Paenibacillus larvae bacteremia in injection drug users. Emerg Infect Dis. 2010;16(3):487–9.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Lockhart PB, Brennan MT, Sasser HC, Fox PC, Paster BJ, Bahrani-Mougeot FK. Bacteremia associated with toothbrushing and dental extraction. Circulation. 2008;117:3118–25.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Forner L, Larsen T, Kilian M, Holmstrup P. Incidence of bacteremia after chewing, tooth brushing and scaling in individuals with periodontal inflammation. J Clin Periodontol. 2006;33(6):401–7.PubMedGoogle Scholar
  30. 30.
    MacFarlane TW, Samaranayake LP. Clinical oral microbiology. London: Wright; 1989.Google Scholar
  31. 31.
    Hiffajee AD, Socransky SS, Dzink JL, et al. Clinical, microbiological and immunological features of subjects with destructive periodontal diseases. J Clin Periodontol. 1988;15:240–6.Google Scholar
  32. 32.
    Goodson JM, Tanner AC, Haffajec AD, et al. Patterns of progression and regression of advanced destructive periodontal disease. J Clin Periodontol. 1982;9:472–81.PubMedGoogle Scholar
  33. 33.
    Paster BJ, Olsen I, Aas JA, Dewhirst FE. The breadth of bacterial diversity in the human periodontal pocket and other oral sites. Periodontol. 2006;42:80–7.Google Scholar
  34. 34.
    Little JW, Falace DA, Miller CS, Rhodus NL. Infective endocarditis. In: Dental management of the medically compromised patient. 6th edition. Toronto: Mosby, Inc.; 2002. Pp. 21–51.Google Scholar
  35. 35.
    Tomas I, Alvarez M, Limeres J, Potel C, Medina J, Diz P. Prevalence, duration and aetiology of bacteraemia following dental extractions. Oral Dis. 2007;13(1):56–62.PubMedGoogle Scholar
  36. 36.
    Takai S, Kuriyama T, Yanagisawa M, Nakagawa K, Karasawa T. Incidence and bacteriology of bacteremia associated with various oral and maxillofacial surgical procedures. Oral Surg Oral Med Oral Pathol Oral Radiol Endond. 2005;99(3):292–8.Google Scholar
  37. 37.
    Roberts GJ, Holzel HS, Sury MR, Simmons NA, Gardner P, Longhurst P. Dental bacteremia in children. Pediatr Cardiol. 1997;18(1):24–7.PubMedGoogle Scholar
  38. 38.
    Okabe K, Nakagawa K, Yamamoto E. Factors affecting the occurrence of bacteremia associated with tooth extraction. Int J Oral Maxillofac Surg. 1995;24(3):239–42.PubMedGoogle Scholar
  39. 39.
    Hartzell JD, Torres D, Kim P, Wortmann G. Incidence of bacteremia after routine tooth brushing. Am J Med Sci. 2005;329:178–80.PubMedGoogle Scholar
  40. 40.
    Hall G, Hedstrom SA, Heimdahl A, Nord CE. Prophylactic administration of penicillins for endocarditis does not reduce the incidence of postextraction bacteremia. Clin Infect Dis. 1993;17:188–94.PubMedGoogle Scholar
  41. 41.
    Heimdahl A, Hall G, Hedberg M, Sandberg H, Söder PO, Tunér K, et al. Detection and quantitation by lysis-filtration of bacteremia after different oral surgical procedures. J Clin Microbiol. 1990;28:2205–9.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Sconyers JR, Crawford JJ, Moriarty JD. Relationship of bacteremia to toothbrushing in patients with periodontitis. J Am Dent Assoc. 1973;87:616–22.PubMedGoogle Scholar
  43. 43.
    Hillman RS, Ault KA, Rinder HM. Hematology in clinical practice: a guide to diagnosis and management. 4th ed. New York: McGraw-Hill Professional; 2005.Google Scholar
  44. 44.
    Pierigè F, Serafini S, Rossi L, Magnani M. Cell-based drug delivery. Adv Drug Deliv Rev. 2008;60(2):286–95.PubMedGoogle Scholar
  45. 45.
    Marieb EN, Hoehn K. The cardiovascular system: blood vessels. Human anatomy & physiology. 9th ed. Pearson Education, Inc.; 2013.Google Scholar
  46. 46.
    Bicker H, Höflich C, Wolk K, Vogt K, Volk H-D, Sabat R. A simple assay to measure phagocytosis of live bacteria. Clin Chem. 2008;54(5):911–5.PubMedGoogle Scholar
  47. 47.
    Lee C-Y, Herant M, Heinrich V. Target-specific mechanics of phagocytosis: protrusive neutrophil response to zymosan differs from the uptake of antibody-tagged pathogens. J Cell Sci. 2010;124:1106–14.Google Scholar
  48. 48.
    Herant M, Heinrich V, Dembo M. Mechanics of neutrophil phagocytosis: experiments and quantitative models. J Cell Sci. 2006;119:1903–13.PubMedGoogle Scholar
  49. 49.
    Dewitt S, Hallett M. Leukocyte membrane “expansion”: a central mechanism for leukocyte extravasation. J Leukoc Biol. 2007;81:1160–4.PubMedGoogle Scholar
  50. 50.
    Minasyan H. Erythrocyte and leukocyte: two partners in bacteria killing. Int Rev Immunol. 2014;33(6):490–7.PubMedGoogle Scholar
  51. 51.
    Minasyan H. Mechanisms and pathways for the clearance of bacteria from blood circulation in health and disease. Pathophysiology. 2016;23:61–6.PubMedGoogle Scholar
  52. 52.
    Minasyan H. Erythrocyte bacteria killer and bacteria pray. Int J Immunol Spec Issue: Antibacterial Cell Humoral Immun. 2014;2(5–1):1–7.Google Scholar
  53. 53.
    Minasyan H. Erythrocyte and blood antibacterial defense. Eur J Microbiol Immunol. 2014;4(2):138–43.Google Scholar
  54. 54.
    Minasyan H. Erythrocyte is the first line of blood antibacterial defense. J Clin Cell Immunol. 2014;5(5):165.Google Scholar
  55. 55.
    Burwen SJ, Satir BH. Plasma membrane folds on mast cell surface. J Cell Biol. 1977;74:690–7.PubMedGoogle Scholar
  56. 56.
    Wheater PL, Stevens A. Wheater’s basic histopathology: a color atlas and text. Edinburgh: Churchill Livingstone; 2000.Google Scholar
  57. 57.
    Gordon S. Macrophages and the immune response. In: Paul EW, editor. Fundamental immunology. Philadelphia: Lippincott-Raven; 1999. p. 533–45.Google Scholar
  58. 58.
    Pillay J, den Brober I, Vrisecoop N, Kwast ML. In vivo labeling with H202 reveals a human neutrophil lifespan of 5.4 days. Blood. 2010;116(4):625–7.PubMedGoogle Scholar
  59. 59.
    Harrison KL. Fetal erythrocyte lifespan. J Paediatr Child Health. 1979;15(2):96–7.Google Scholar
  60. 60.
    Lahoz-Beneytez J, Elemans M, Zhang Y, Raya Ahmed R, Salam A, Block M, et al. Human neutrophil kinetics: modeling of stable isotope labeling data supports short blood neutrophil half-lives. Blood. 2016;127:3431–8.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Maiden M CJ, Caugant D A. The population biology of Neisseria meningitidis: implications for meningococcal disease, epidemiology and control. In Frosch M, Maiden MCJ, editors. Handbook of meningococcal disease. Wiley-VCH; 2006. Pp.184–91.Google Scholar
  62. 62.
    Stohl EA, Seifert HS. Neisseria gonorrhoeae DNA recombination and repair enzymes protect against oxidative damage caused by hydrogen peroxide. J Bacteriol. 2006;188(21):7645–51.PubMedPubMedCentralGoogle Scholar
  63. 63.
    North RJ, Jung YJ. Immunity to tuberculosis. Annu Rev Immunol. 2004;22:599–23.PubMedGoogle Scholar
  64. 64.
    Manca C, Reed MB, Freeman S, Mathema B, Kreiswirth B, Barry CE, et al. Differential monocyte activation underlies strain-specific Mycobacterium tuberculosis pathogenesis. Infect Immun. 2004;72(9):5511–4.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Densen P, Mandell GL. Phagocyte strategy vs. microbial tactics. J Infect Dis. 1980;2:817.Google Scholar
  66. 66.
    Tilney LG, Portnoy DA. Actin filaments and the growth, movement, and spread of the intracellular bacterial parasite, Listeria monocytogenes. J Cell Biol. 1989;109:1597–605.PubMedGoogle Scholar
  67. 67.
    Schutze GE, Buckingham SC, Marshall GS, et al. Human monocytic ehrlichiosis in children. Pediatr Infect Dis J. 2007;26(6):475–9.PubMedGoogle Scholar
  68. 68.
    Ernst JD, Stendahl O, editors. Phagocytosis of bacteria and bacterial pathogenicity. New York: Cambridge University Press; 2006.Google Scholar
  69. 69.
    Wilson WW, Wade MM, Holman SC, Champlin FR. Status of methods for assessing bacterial cell surface charge properties based on zeta potential measurements. J Microbiol Methods. 2001;43(3):153–64.PubMedGoogle Scholar
  70. 70.
    Dziubakiewicz E, Hrynkiewicz K, Walzyk M, Buszewski B. Study of charge distribution on the surface of biocolloids. Colloids Surf B: Biointerfaces. 2013;104:122–7.PubMedGoogle Scholar
  71. 71.
    Ayala-Torres, Hernández N, Galeano, Novoa-Aponte L, Soto C-Y. Zeta potential as a measure of the surface charge of mycobacterial cells. Ann Microbiol. 2014;64(3):1189–95.Google Scholar
  72. 72.
    Kambara M, Nomura K, Miyake T, Uemura M, Noshi H, Konishi K. Zeta potential of oral bacteria (streptococci). J Osaka Dent Univ. 1989;23(1):39–43.PubMedGoogle Scholar
  73. 73.
    Soni KA, Balasubramanian AK, Beskok A, Pillai SD. Zeta potential of selected bacteria in drinking water when dead, starved, or exposed to minimal and rich culture media. Curr Microbiol. 2008;56(1):93–7.PubMedGoogle Scholar
  74. 74.
    Alizadehrad D, Imai Y, Nakaaki K, Ishikawa T, Yamaguchi T. Quantification of red blood cell deformation at high-hematocrit blood flow in microvessels. J Biomech. 2012;45(15):2684–9.PubMedGoogle Scholar
  75. 75.
    Pfafferott C, Nash GB, Meiselman HJ. Red blood cell deformation in shear flow. Effects of internal and external phase viscosity and of in vivo aging. Biophys J. 1985;47(5):695–704.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Vatansever F, de Melo WCMA, Avci P, Vecchio D, Sadasivam M, Gupta A, et al. Antimicrobial strategies centered around reactive oxygen species - bactericidal antibiotics, photodynamic therapy and beyond. FEMS Microbiol Rev. 2013;37(6):955–89.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Wan J, Forsyth AM, Stone HA. Red blood cell dynamics: from cell deformation to ATP release. Integr Biol (Camb). 2011;3(10):972–81.Google Scholar
  78. 78.
    Ellsworth ML, Ellis CG, Goldman D, Stephenson AH, Dietrich HH, Sprague RS. Erythrocytes: Oxygen sensors and modulators of vascular tone in regions of low PO2. Physiology (Bethesda). 2009;24:107–16.Google Scholar
  79. 79.
    Bogdan C. Oxidative burst without phagocytes: the role of respiratory proteins. Nat Immunol. 2007;8:1029–31.PubMedGoogle Scholar
  80. 80.
    Jiang N, Tan NS, Ho B, Ding JL. Respiratory protein–generated reactive oxygen species as an antimicrobial strategy. Nat Immunol. 2007;8:1114–22.PubMedGoogle Scholar
  81. 81.
    Biozzi G, Benacerraf B, Halpern BN. Quantitative study of the granulopoetic activity of the reticuloendothelial system II. A study of the kinetics of the granulopoetic activity of the RES in relation to the dose of carbon injected. Relationship between the weight of the organs and their activity. Br J Exp Pathol. 1953;34:441–8.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Wanless IR. Physioanatomic considerations. In: Schiff ER, Sorrell MF, Maddrey WC, editors. Schiff’s diseases of the liver. Philadelphia: Lippincott-Raven; 1999. p. 3–38.Google Scholar
  83. 83.
    Mebius RE, Kraal G. Structure and function of the spleen. Nat Rev Immunol. 2005;5:606–16.PubMedGoogle Scholar
  84. 84.
    Bowdler A. The complete spleen: structure, function and clinical disorders. 2nd ed. New Jersey: Humana Press; 2002.Google Scholar
  85. 85.
    Lawrence G. The hypodermic syringe. Lancet. 2002;359(9311):1074.Google Scholar
  86. 86.
    Muller WA. Mechanisms of leukocyte transendothelial migration. Annu Rev Pathol: Mech Dis. 2011;6:323–44.Google Scholar
  87. 87.
    Nourshargh S, Alon R. Leukocyte migration into inflamed tissues. Immunity. 2014;41(5):694–707.PubMedGoogle Scholar
  88. 88.
    Muller WA. Leukocyte-endothelial-cell interactions in leukocyte transmigration and the inflammatory response. Trends Immunol. 2003;24:326–33.Google Scholar
  89. 89.
    Ley K, Laudanna C, Cybulsky MI, Nourshargh S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007;7:678–89.PubMedGoogle Scholar
  90. 90.
    Muller WA. PECAM: regulating the start of diapedesis. In: Ley K, editor. Adhesion molecules: function and inhibition. Basel: Birkhauser Verlag AG; 2007. p. 201–20.Google Scholar
  91. 91.
    Carman CV, Springer TA. Trans-cellular migration: cell-cell contacts get intimate. Curr Opin Cell Biol. 2008;20:533–40.PubMedPubMedCentralGoogle Scholar
  92. 92.
    Monk PN, Scola AM, Madala P, Fairlie DP. Function, structure and therapeutic potential of complement C5a receptors. Br J Pharmacol. 2007;152:429–48.PubMedPubMedCentralGoogle Scholar
  93. 93.
    Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013;496:445–55.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Gregory SH, Wing EJ. Neutrophil-Kupffer-cell interaction in host defenses to systemic infections. Immunol Today. 1998;19(11):507–10.PubMedGoogle Scholar
  95. 95.
    Bilzer M, Roggel F, Gerbes AL. Role of Kupffer cells in host defense and liver disease. Liver Int. 2006;26(10):1175–86.PubMedGoogle Scholar
  96. 96.
    Liaskou E, Wilson DV, Oo YH. Innate immune cells in liver inflammation. Mediators of Inflammation,Volume 2012 (2012), Article ID 949157, 21 pages.Google Scholar
  97. 97.
    Dhainaut JF, Marin N, Mignon A, Vinsonneau C. Hepatic response to sepsis: interaction between coagulation and inflammatory processes. Crit Care Med. 2001;29(7):42–7.Google Scholar
  98. 98.
    Gregory SH, Wing EJ. Neutrophil-Kupffer cell interaction: a critical component of host defenses to systemic bacterial infections. J Leukoc Biol. 2002;72(2):239–48.PubMedGoogle Scholar
  99. 99.
    Holub M, Cheng CW, Mott S, Wintermeyer P, van Rooijen N, Gregory SH. Neutrophils sequestered in the liver the proinflammatory response of Kupffer cells to systemic bacterial infection suppress. J Immunol. 2009;183(5):3309–16.PubMedGoogle Scholar
  100. 100.
    Kuo CH, Changchien CS, Yang CY, Sheen IS, Liaw YF. Bacteremia in patients with cirrhosis of the liver. Liver. 1991;11(6):334–9.PubMedGoogle Scholar
  101. 101.
    Almdal T, Skinhøj P, Friis H. Bacteremia in patients suffering from cirrhosis. Infection. 1986;14(2):68–70.PubMedGoogle Scholar
  102. 102.
    Shizuma T, Obata H, Hashimoto E, Shiratori K. Relationship between bacteremia and severity of liver dysfunction in patients with liver cirrhosis. Kanzo. 2003;44(12):641–8.Google Scholar
  103. 103.
    Altamura M, Caradonna L, Amati L, Pellegrino NM, Urgesi G, Miniello S. Splenectomy and sepsis: the role of the spleen in the immune-mediated bacterial clearance. Immunopharmacol Immunotoxicol. 2001;23(2):153–61.PubMedGoogle Scholar
  104. 104.
    Lynch AM, Kapila R. Overwhelming postsplenectomy infection. Infect Dis Clin N Am. 1996;10:693–707.Google Scholar
  105. 105.
    Davidson RN, Wall RA. Prevention and management of infections in patients without a spleen. Clin Microbiol Infect. 2001;7:657–60.PubMedGoogle Scholar
  106. 106.
    Ejstrud P, Kristensen B, Hansen JB, Madsen KM, Schønheyder HC, Sørensen HT. Risk and patterns of bacteraemia after splenectomy: a population-based study. Scand J Infect Dis. 2000;32(5):521–5.PubMedGoogle Scholar
  107. 107.
    Styrt B. Infection associated with asplenia: risks, mechanisms, and prevention. Am J Med. 1990;88:33–42.Google Scholar
  108. 108.
    Bisharat N, Omari H, Lavi I, Raz R. Risk of infection and death among post-splenectomy patients. J Inf Secur. 2001;43:182–6.Google Scholar
  109. 109.
    Sickle Cell Association of America. Research and screening (http://www.sicklecelldisease.org/index.cfm?page=research-screening).
  110. 110.
    Katz SC, Pachter HL. Indications for splenectomy. Am Surg. 2006;72:565–80.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Hayk Minasyan
    • 1
  1. 1.YerevanArmenia

Personalised recommendations