Integrin αDβ2 influences cerebral edema, leukocyte accumulation and neurologic outcomes in experimental severe malaria


Autoři: Isaclaudia G. de Azevedo-Quintanilha aff001;  Adriana Vieira-de-Abreu aff001;  André C. Ferreira aff001;  Patricia A. Reis aff001;  Tathiany I. Silva aff001;  Danielle de O. Nascimento aff001;  Robert A. Campbell aff002;  Vanessa Estato aff001;  Andrew S. Weyrich aff002;  Patrícia T. Bozza aff001;  Guy A. Zimmerman aff002;  Hugo C. Castro-Faria-Neto aff001
Působiště autorů: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil aff001;  Department of Internal Medicine and Program in Molecular Medicine, University of Utah, Salt Lake City, Utah, United States of America aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224610

Souhrn

Malaria is an infectious disease of major worldwide clinical importance that causes a variety of severe, or complicated, syndromes including cerebral malaria, which is often fatal. Leukocyte integrins are essential for host defense but also mediate physiologic responses of the innate and adaptive immune systems. We previously showed that targeted deletion of the αD subunit (αD-/-) of the αDβ2 integrin, which is expressed on key leukocyte subsets in mice and humans, leads to absent expression of the integrin heterodimer on murine macrophages and reduces mortality in mice infected with Plasmodium berghei ANKA (P. berghei ANKA). To further identify mechanisms involved in the protective effect of αD deletion in this model of severe malaria we examined wild type C57BL/6 (WT) and αD-/- mice after P. berghei ANKA infection and found that vessel plugging and leukocyte infiltration were significantly decreased in the brains of αD-/- animals. Intravital microscopy demonstrated decreased rolling and adhesion of leukocytes in cerebral vessels of αD-/- mice. Flow cytometry analysis showed decreased T-lymphocyte accumulation in the brains of infected αD-/- animals. Evans blue dye exclusion assays demonstrated significantly less dye extravasation in the brains of αD-/- mice, indicating preserved blood-brain barrier integrity. WT mice that were salvaged from P. berghei ANKA infection by treatment with chloroquine had impaired aversive memory, which was not observed in αD-/- mice. We conclude that deletion of integrin αDβ2 alters the natural course of experimental severe malaria, demonstrating previously unrecognized activities of a key leukocyte integrin in immune-inflammatory responses that mediate cerebral involvement.

Klíčová slova:

Cerebral malaria – Inflammation – Integrins – Malaria – Mouse models – Plasmodium – T cells – White blood cells


Zdroje

1. Phillips MA, Burrows JN, Manyando C, van Huijsduijnen RH, Van Voorhis WC, Wells TNC. Malaria. Nature reviews Disease primers. 2017;3:17050. Epub 2017/08/05. doi: 10.1038/nrdp.2017.50 28770814.

2. White NJ, Pukrittayakamee S, Hien TT, Faiz MA, Mokuolu OA, Dondorp AM. Malaria. Lancet. 2014;383(9918):723–35. Epub 2013/08/21. doi: 10.1016/S0140-6736(13)60024-0 23953767.

3. Craig AG, Khairul MF, Patil PR. Cytoadherence and severe malaria. The Malaysian journal of medical sciences: MJMS. 2012;19(2):5–18. Epub 2012/09/14. 22973133.

4. Idro R, Kakooza-Mwesige A, Asea B, Ssebyala K, Bangirana P, Opoka RO, et al. Cerebral malaria is associated with long-term mental health disorders: a cross sectional survey of a long-term cohort. Malar J. 2016;15:184. Epub 2016/04/01. doi: 10.1186/s12936-016-1233-6 27030124.

5. Ponsford MJ, Medana IM, Prapansilp P, Hien TT, Lee SJ, Dondorp AM, et al. Sequestration and microvascular congestion are associated with coma in human cerebral malaria. J Infect Dis. 2012;205(4):663–71. Epub 2011/12/31. doi: 10.1093/infdis/jir812 22207648.

6. Baruch DI. Adhesive receptors on malaria-parasitized red cells. Baillieres Best Pract Res Clin Haematol. 1999;12(4):747–61. Epub 2000/07/15. doi: 10.1053/beha.1999.0051 10895262.

7. Miller LH, Baruch DI, Marsh K, Doumbo OK. The pathogenic basis of malaria. Nature. 2002;415(6872):673–9. Epub 2002/02/08. doi: 10.1038/415673a 11832955.

8. Mo M, Lee HC, Kotaka M, Niang M, Gao X, Iyer JK, et al. The C-terminal segment of the cysteine-rich interdomain of Plasmodium falciparum erythrocyte membrane protein 1 determines CD36 binding and elicits antibodies that inhibit adhesion of parasite-infected erythrocytes. Infect Immun. 2008;76(5):1837–47. Epub 2008/02/27. doi: 10.1128/IAI.00480-07 18299339.

9. Faille D, Combes V, Mitchell AJ, Fontaine A, Juhan-Vague I, Alessi MC, et al. Platelet microparticles: a new player in malaria parasite cytoadherence to human brain endothelium. FASEB J. 2009;23(10):3449–58. Epub 2009/06/19. doi: 10.1096/fj.09-135822 19535685.

10. Hughes KR, Biagini GA, Craig AG. Continued cytoadherence of Plasmodium falciparum infected red blood cells after antimalarial treatment. Mol Biochem Parasitol. 2010;169(2):71–8. Epub 2009/10/06. doi: 10.1016/j.molbiopara.2009.09.007 19800372.

11. Janes JH, Wang CP, Levin-Edens E, Vigan-Womas I, Guillotte M, Melcher M, et al. Investigating the host binding signature on the Plasmodium falciparum PfEMP1 protein family. PLoS Pathog. 2011;7(5):e1002032. Epub 2011/05/17. doi: 10.1371/journal.ppat.1002032 21573138.

12. Wu Y, Szestak T, Stins M, Craig AG. Amplification of P. falciparum Cytoadherence through induction of a pro-adhesive state in host endothelium. PLoS One. 2011;6(10):e24784. Epub 2011/11/02. doi: 10.1371/journal.pone.0024784 22043276.

13. Urban BC, Roberts DJ. Malaria, monocytes, macrophages and myeloid dendritic cells: sticking of infected erythrocytes switches off host cells. Curr Opin Immunol. 2002;14(4):458–65. Epub 2002/06/29. doi: 10.1016/s0952-7915(02)00368-0 12088680.

14. Schofield L, Grau GE. Immunological processes in malaria pathogenesis. Nat Rev Immunol. 2005;5(9):722–35. Epub 2005/09/03. doi: 10.1038/nri1686 16138104.

15. Ryg-Cornejo V, Nie CQ, Bernard NJ, Lundie RJ, Evans KJ, Crabb BS, et al. NK cells and conventional dendritic cells engage in reciprocal activation for the induction of inflammatory responses during Plasmodium berghei ANKA infection. Immunobiology. 2012. Epub 2012/06/19. doi: 10.1016/j.imbio.2012.05.018 22704523.

16. Faille D, El-Assaad F, Alessi MC, Fusai T, Combes V, Grau GE. Platelet-endothelial cell interactions in cerebral malaria: the end of a cordial understanding. Thromb Haemost. 2009;102(6):1093–102. Epub 2009/12/08. doi: 10.1160/TH09-05-0337 19967139.

17. Combes V, Coltel N, Faille D, Wassmer SC, Grau GE. Cerebral malaria: role of microparticles and platelets in alterations of the blood-brain barrier. Int J Parasitol. 2006;36(5):541–6. Epub 2006/04/08. doi: 10.1016/j.ijpara.2006.02.005 16600245.

18. Gramaglia I, Velez J, Combes V, Grau GE, Wree M, van der Heyde HC. Platelets activate a pathogenic response to blood-stage Plasmodium infection but not a protective immune response. Blood. 2017. Epub 2017/01/18. doi: 10.1182/blood-2016-08-733519 28096086.

19. Apinjoh TO, Anchang-Kimbi JK, Njua-Yafi C, Mugri RN, Ngwai AN, Rockett KA, et al. Association of cytokine and Toll-like receptor gene polymorphisms with severe malaria in three regions of Cameroon. PLoS One. 2013;8(11):e81071. Epub 2013/12/07. doi: 10.1371/journal.pone.0081071 24312262.

20. Hansen DS. Inflammatory responses associated with the induction of cerebral malaria: lessons from experimental murine models. PLoS Pathog. 2012;8(12):e1003045. Epub 2013/01/10. doi: 10.1371/journal.ppat.1003045 23300435.

21. Hunt NH, Ball HJ, Hansen AM, Khaw LT, Guo J, Bakmiwewa S, et al. Cerebral malaria: gamma-interferon redux. Frontiers in cellular and infection microbiology. 2014;4:113. Epub 2014/09/02. doi: 10.3389/fcimb.2014.00113 25177551.

22. Souza MC, Padua TA, Henriques MG. Endothelial-Leukocyte Interaction in Severe Malaria: Beyond the Brain. Mediators of inflammation. 2015;2015:168937. Epub 2015/10/23. doi: 10.1155/2015/168937 26491221.

23. Sahu U, Sahoo PK, Kar SK, Mohapatra BN, Ranjit M. Association of TNF level with production of circulating cellular microparticles during clinical manifestation of human cerebral malaria. Hum Immunol. 2013;74(6):713–21. Epub 2013/03/06. doi: 10.1016/j.humimm.2013.02.006 23459075.

24. Harris ES, McIntyre TM, Prescott SM, Zimmerman GA. The leukocyte integrins. J Biol Chem. 2000;275(31):23409–12. Epub 2000/05/10. doi: 10.1074/jbc.R000004200 10801898.

25. Ockenhouse CF, Tegoshi T, Maeno Y, Benjamin C, Ho M, Kan KE, et al. Human vascular endothelial cell adhesion receptors for Plasmodium falciparum-infected erythrocytes: roles for endothelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1. J Exp Med. 1992;176(4):1183–9. Epub 1992/10/01. doi: 10.1084/jem.176.4.1183 1383378.

26. Berendt AR, Tumer GD, Newbold CI. Cerebral malaria: the sequestration hypothesis. Parasitol Today. 1994;10(10):412–4. Epub 1994/01/01. doi: 10.1016/0169-4758(94)90238-0 15275553.

27. Reis PA, Estato V, da Silva TI, d’Avila JC, Siqueira LD, Assis EF, et al. Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria. PLoS Pathog. 2012;8(12):e1003099. doi: 10.1371/journal.ppat.1003099 23300448.

28. Bao LQ, Nhi DM, Huy NT, Kikuchi M, Yanagi T, Hamano S, et al. Splenic CD11c+ cells derived from semi-immune mice protect naive mice against experimental cerebral malaria. Malar J. 2015;14:23. Epub 2015/01/30. doi: 10.1186/s12936-014-0533-y 25626734.

29. Pichyangkul S, Saengkrai P, Yongvanitchit K, Heppner DG, Kyle DE, Webster HK. Regulation of leukocyte adhesion molecules CD11b/CD18 and leukocyte adhesion molecule-1 on phagocytic cells activated by malaria pigment. Am J Trop Med Hyg. 1997;57(4):383–8. Epub 1997/11/05. doi: 10.4269/ajtmh.1997.57.383 9347950.

30. Barczyk M, Carracedo S, Gullberg D. Integrins. Cell and tissue research. 2010;339(1):269–80. Epub 2009/08/21. doi: 10.1007/s00441-009-0834-6 19693543.

31. Lowell CA, Mayadas TN. Overview: studying integrins in vivo. Methods Mol Biol. 2012;757:369–97. Epub 2011/09/13. doi: 10.1007/978-1-61779-166-6_22 21909923.

32. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell. 2002;110(6):673–87. Epub 2002/09/26. doi: 10.1016/s0092-8674(02)00971-6 12297042.

33. Harris ES, Weyrich AS, Zimmerman GA. Lessons from rare maladies: leukocyte adhesion deficiency syndromes. Curr Opin Hematol. 2013;20(1):16–25. Epub 2012/12/05. 23207660.

34. Danilenko DM, Rossitto PV, Van der Vieren M, Le Trong H, McDonough SP, Affolter VK, et al. A novel canine leukointegrin, alpha d beta 2, is expressed by specific macrophage subpopulations in tissue and a minor CD8+ lymphocyte subpopulation in peripheral blood. J Immunol. 1995;155(1):35–44. Epub 1995/07/01. 7541420.

35. el-Gabalawy H, Canvin J, Ma GM, Van der Vieren M, Hoffman P, Gallatin M, et al. Synovial distribution of alpha d/CD18, a novel leukointegrin. Comparison with other integrins and their ligands. Arthritis and rheumatism. 1996;39(11):1913–21. Epub 1996/11/01. doi: 10.1002/art.1780391119 8912515.

36. Miyazaki Y, Vieira-de-Abreu A, Harris ES, Shah AM, Weyrich AS, Castro-Faria-Neto HC, et al. Integrin alphaDbeta2 (CD11d/CD18) is expressed by human circulating and tissue myeloid leukocytes and mediates inflammatory signaling. PLoS One. 2014;9(11):e112770. Epub 2014/11/22. doi: 10.1371/journal.pone.0112770 25415295.

37. Miyazaki Y, Bunting M, Stafforini DM, Harris ES, McIntyre TM, Prescott SM, et al. Integrin alphaDbeta2 is dynamically expressed by inflamed macrophages and alters the natural history of lethal systemic infections. J Immunol. 2008;180(1):590–600. Epub 2007/12/22. doi: 10.4049/jimmunol.180.1.590 18097061.

38. de Azevedo-Quintanilha IG, Vieira-de-Abreu A, Ferreira AC, Nascimento DO, Siqueira AM, Campbell RA, et al. Integrin alphaDbeta2 (CD11d/CD18) mediates experimental malaria-associated acute respiratory distress syndrome (MA-ARDS). Malar J. 2016;15(1):393. Epub 2016/07/31. doi: 10.1186/s12936-016-1447-7 27473068.

39. Aziz MH, Cui K, Das M, Brown KE, Ardell CL, Febbraio M, et al. The Upregulation of Integrin alphaDbeta2 (CD11d/CD18) on Inflammatory Macrophages Promotes Macrophage Retention in Vascular Lesions and Development of Atherosclerosis. J Immunol. 2017;198(12):4855–67. Epub 2017/05/14. doi: 10.4049/jimmunol.1602175 28500072.

40. Weaver LC, Bao F, Dekaban GA, Hryciw T, Shultz SR, Cain DP, et al. CD11d integrin blockade reduces the systemic inflammatory response syndrome after traumatic brain injury in rats. Exp Neurol. 2015;271:409–22. Epub 2015/07/15. doi: 10.1016/j.expneurol.2015.07.003 26169930.

41. Geremia NM, Bao F, Rosenzweig TE, Hryciw T, Weaver L, Dekaban GA, et al. CD11d Antibody Treatment Improves Recovery in Spinal Cord-Injured Mice. Journal of neurotrauma. 2012;29(3):539–50. Epub 2011/11/03. doi: 10.1089/neu.2011.1976 22044160.

42. Bao F, Dekaban GA, Weaver LC. Anti-CD11d antibody treatment reduces free radical formation and cell death in the injured spinal cord of rats. J Neurochem. 2005;94(5):1361–73. Epub 2005/07/05. doi: 10.1111/j.1471-4159.2005.03280.x 15992367.

43. Van den Steen PE, Deroost K, Deckers J, Van Herck E, Struyf S, Opdenakker G. Pathogenesis of malaria-associated acute respiratory distress syndrome. Trends Parasitol. 2013. Epub 2013/06/08. doi: 10.1016/j.pt.2013.04.006 23742967.

44. Thumwood CM, Hunt NH, Clark IA, Cowden WB. Breakdown of the blood-brain barrier in murine cerebral malaria. Parasitology. 1988;96 (Pt 3):579–89. Epub 1988/06/01. doi: 10.1017/s0031182000080203 2457201.

45. Beeton C, Chandy KG. Isolation of mononuclear cells from the central nervous system of rats with EAE. Journal of visualized experiments: JoVE. 2007;(10):527. Epub 2008/11/08. doi: 10.3791/527 18989401.

46. Irani DN, Griffin DE. Isolation of brain parenchymal lymphocytes for flow cytometric analysis. Application to acute viral encephalitis. Journal of immunological methods. 1991;139(2):223–31. Epub 1991/06/03. doi: 10.1016/0022-1759(91)90192-i 1675228.

47. Araujo CV, Campbell C, Goncalves-de-Albuquerque CF, Molinaro R, Cody MJ, Yost CC, et al. A Ppargamma Agonist Enhances Bacterial Clearance Through Neutrophil Extracellular Trap Formation and Improves Survival in Sepsis. Shock. 2015. Epub 2015/12/01. doi: 10.1097/SHK.0000000000000520 26618986.

48. Reis PA, Comim CM, Hermani F, Silva B, Barichello T, Portella AC, et al. Cognitive dysfunction is sustained after rescue therapy in experimental cerebral malaria, and is reduced by additive antioxidant therapy. PLoS Pathog. 2010/06/30 ed2010. p. e1000963. doi: 10.1371/journal.ppat.1000963 20585569

49. Lackner P, Beer R, Heussler V, Goebel G, Rudzki D, Helbok R, et al. Behavioural and histopathological alterations in mice with cerebral malaria. Neuropathology and applied neurobiology. 2006;32(2):177–88. Epub 2006/04/08. doi: 10.1111/j.1365-2990.2006.00706.x 16599946.

50. Irwin S. Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacologia. 1968;13(3):222–57. Epub 1968/09/20. doi: 10.1007/bf00401402 5679627.

51. Franke-Fayard B, Janse CJ, Cunha-Rodrigues M, Ramesar J, Buscher P, Que I, et al. Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration. Proc Natl Acad Sci U S A. 2005;102(32):11468–73. Epub 2005/07/30. doi: 10.1073/pnas.0503386102 16051702.

52. Hansen DS, Stewart CR, Jaworowski A, de-Koning Ward TF. Advances in infection and immunity: from bench to bedside. Immunol Cell Biol. 2012;90(8):751–4. Epub 2012/08/01. doi: 10.1038/icb.2012.40 22846710.

53. Neill AL, Chan-Ling T, Hunt NH. Comparisons between microvascular changes in cerebral and non-cerebral malaria in mice, using the retinal whole-mount technique. Parasitology. 1993;107 (Pt 5):477–87. Epub 1993/12/01. doi: 10.1017/s0031182000068050 8295787.

54. Jennings VM, Lal AA, Hunter RL. Evidence for multiple pathologic and protective mechanisms of murine cerebral malaria. Infect Immun. 1998;66(12):5972–9. Epub 1998/11/24. 9826380.

55. Bostrom S, Giusti P, Arama C, Persson JO, Dara V, Traore B, et al. Changes in the levels of cytokines, chemokines and malaria-specific antibodies in response to Plasmodium falciparum infection in children living in sympatry in Mali. Malar J. 2012;11:109. Epub 2012/04/07. doi: 10.1186/1475-2875-11-109 22480186.

56. Hunt NH, Grau GE. Cytokines: accelerators and brakes in the pathogenesis of cerebral malaria. Trends Immunol. 2003;24(9):491–9. Epub 2003/09/12. doi: 10.1016/s1471-4906(03)00229-1 12967673.

57. Schofield L. Intravascular infiltrates and organ-specific inflammation in malaria pathogenesis. Immunol Cell Biol. 2007;85(2):130–7. Epub 2007/03/09. doi: 10.1038/sj.icb.7100040 17344907.

58. Dorovini-Zis K, Schmidt K, Huynh H, Fu W, Whitten RO, Milner D, et al. The neuropathology of fatal cerebral malaria in malawian children. Am J Pathol. 2011;178(5):2146–58. Epub 2011/04/26. doi: 10.1016/j.ajpath.2011.01.016 21514429.

59. Pai S, Qin J, Cavanagh L, Mitchell A, El-Assaad F, Jain R, et al. Real-time imaging reveals the dynamics of leukocyte behaviour during experimental cerebral malaria pathogenesis. PLoS Pathog. 2014;10(7):e1004236. Epub 2014/07/18. doi: 10.1371/journal.ppat.1004236 25033406.

60. Boivin MJ, Bangirana P, Byarugaba J, Opoka RO, Idro R, Jurek AM, et al. Cognitive impairment after cerebral malaria in children: a prospective study. Pediatrics. 2007;119(2):e360–6. Epub 2007/01/17. doi: 10.1542/peds.2006-2027 17224457.

61. Bangirana P, Allebeck P, Boivin MJ, John CC, Page C, Ehnvall A, et al. Cognition, behaviour and academic skills after cognitive rehabilitation in Ugandan children surviving severe malaria: a randomised trial. BMC neurology. 2011;11:96. Epub 2011/08/06. doi: 10.1186/1471-2377-11-96 21816079.

62. Bangirana P, Opoka RO, Boivin MJ, Idro R, Hodges JS, John CC. Neurocognitive domains affected by cerebral malaria and severe malarial anemia in children. Learning and individual differences. 2016;46:38–44. Epub 2016/05/24. doi: 10.1016/j.lindif.2015.01.010 27212870.

63. Ssenkusu JM, Hodges JS, Opoka RO, Idro R, Shapiro E, John CC, et al. Long-term Behavioral Problems in Children With Severe Malaria. Pediatrics. 2016;138(5). Epub 2016/12/13. doi: 10.1542/peds.2016-1965 27940786 conflicts of interest to disclose.

64. Wassmer SC, Taylor TE, Rathod PK, Mishra SK, Mohanty S, Arevalo-Herrera M, et al. Investigating the Pathogenesis of Severe Malaria: A Multidisciplinary and Cross-Geographical Approach. Am J Trop Med Hyg. 2015;93(3 Suppl):42–56. Epub 2015/08/12. doi: 10.4269/ajtmh.14-0841 26259939.

65. Cowman AF, Healer J, Marapana D, Marsh K. Malaria: Biology and Disease. Cell. 2016;167(3):610–24. Epub 2016/10/22. doi: 10.1016/j.cell.2016.07.055 27768886.

66. Cunnington AJ, Walther M, Riley EM. Piecing together the puzzle of severe malaria. Sci Transl Med. 2013;5(211):211ps18. Epub 2013/11/15. doi: 10.1126/scitranslmed.3007432 24225942.

67. Wassmer SC, Grau GE. Severe malaria: what’s new on the pathogenesis front? Int J Parasitol. 2017;47(2–3):145–52. Epub 2016/09/28. doi: 10.1016/j.ijpara.2016.08.002 27670365.

68. de Souza JB, Hafalla JC, Riley EM, Couper KN. Cerebral malaria: why experimental murine models are required to understand the pathogenesis of disease. Parasitology. 2010;137(5):755–72. Epub 2009/12/24. doi: 10.1017/S0031182009991715 20028608.

69. Craig AG, Grau GE, Janse C, Kazura JW, Milner D, Barnwell JW, et al. The role of animal models for research on severe malaria. PLoS Pathog. 2012;8(2):e1002401. Epub 2012/02/10. doi: 10.1371/journal.ppat.1002401 22319438.

70. Bao F, Shultz SR, Hepburn JD, Omana V, Weaver LC, Cain DP, et al. A CD11d monoclonal antibody treatment reduces tissue injury and improves neurological outcome after fluid percussion brain injury in rats. Journal of neurotrauma. 2012;29(14):2375–92. Epub 2012/06/09. doi: 10.1089/neu.2012.2408 22676851.

71. Shultz SR, Bao F, Weaver LC, Cain DP, Brown A. Treatment with an anti-CD11d integrin antibody reduces neuroinflammation and improves outcome in a rat model of repeated concussion. J Neuroinflammation. 2013;10:26. Epub 2013/02/19. doi: 10.1186/1742-2094-10-26 23414334.

72. Nacer A, Movila A, Baer K, Mikolajczak SA, Kappe SH, Frevert U. Neuroimmunological blood brain barrier opening in experimental cerebral malaria. PLoS Pathog. 2012;8(10):e1002982. Epub 2012/11/08. doi: 10.1371/journal.ppat.1002982 23133375.

73. Rondina MT, Weyrich AS, Zimmerman GA. Platelets as cellular effectors of inflammation in vascular diseases. Circ Res. 2013;112(11):1506–19. Epub 2013/05/25. doi: 10.1161/CIRCRESAHA.113.300512 23704217.

74. Yakubenko VP, Yadav SP, Ugarova TP. Integrin alphaDbeta2, an adhesion receptor up-regulated on macrophage foam cells, exhibits multiligand-binding properties. Blood. 2006;107(4):1643–50. Epub 2005/10/22. doi: 10.1182/blood-2005-06-2509 16239428.

75. Yakubenko VP, Belevych N, Mishchuk D, Schurin A, Lam SC, Ugarova TP. The role of integrin alpha D beta2 (CD11d/CD18) in monocyte/macrophage migration. Exp Cell Res. 2008;314(14):2569–78. Epub 2008/07/16. doi: 10.1016/j.yexcr.2008.05.016 18621369.

76. Van der Vieren M, Le Trong H, Wood CL, Moore PF, St John T, Staunton DE, et al. A novel leukointegrin, alpha d beta 2, binds preferentially to ICAM-3. Immunity. 1995;3(6):683–90. Epub 1995/12/01. doi: 10.1016/1074-7613(95)90058-6 8777714.

77. Wu H, Rodgers JR, Perrard XY, Perrard JL, Prince JE, Abe Y, et al. Deficiency of CD11b or CD11d results in reduced staphylococcal enterotoxin-induced T cell response and T cell phenotypic changes. J Immunol. 2004;173(1):297–306. Epub 2004/06/24. doi: 10.4049/jimmunol.173.1.297 15210787.

78. Ohayon A, Golenser J, Sinay R, Tamir A, Altman A, Pollack Y, et al. Protein kinase C theta deficiency increases resistance of C57BL/6J mice to Plasmodium berghei infection-induced cerebral malaria. Infect Immun. 2010;78(10):4195–205. Epub 2010/07/28. doi: 10.1128/IAI.00465-10 20660606.


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