title: Oxidation of hemoglobin and redistribution of band 3 promote erythrophagocytosis in visceral leishmaniasis.
abstract: In visceral leishmaniasis (VL), oxidative assault on erythrocytes perturbs their cellular environment and makes them vulnerable to premature hemolysis. In this study, we assessed the contribution of oxidation-induced modifications of hemoglobin and membrane protein band 3 in the reduced survival of red cells in VL. Oxidative transformation of oxyhemoglobin to hemichrome enhanced its interaction with erythrocyte membrane in the infected animals. Association between denatured globin and band 3 contributed to the formation of insoluble copolymer of macromolecular dimension. Disulfide bonding appeared to be necessary in the making of high molecular weight aggregates during copolymerization. Hemichrome induced clustering of band 3 promoted generation of epitopes on erythrocyte cell surface. This provided a signal favoring immunologic recognition of redistributed band 3 by autologous IgG followed by erythrophagocytosis. An eventual outcome of the sequence of events pointed to early removal of affected red cells from circulation during the disease.
authors.affiliation: Department of Physiology, Indian Institute of Chemical Biology, CSIR, Kolkata, India.
authors.forename: Sudipa
authors.initials: S
authors.lastname: Saha Roy
authors.forename: Kaustav Dutta
authors.initials: KD
authors.lastname: Chowdhury
authors.forename: Gargi
authors.initials: G
authors.lastname: Sen
authors.forename: Tuli
authors.initials: T
authors.lastname: Biswas
mesh_terms: D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D006420:Hemeproteins / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D006461:Hemolysis / Q000502:physiology*; D007898:Leishmaniasis, Visceral / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D010084:Oxidation-Reduction; D010587:Phagocytosis / Q000502:physiology*
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D006420:Hemeproteins; D006454:Hemoglobins; C001332:hemichrome
references.citation: J Biol Chem. 1989 Apr 15;264(11):6438-46
references.pmid: 2649501
references.citation: Br J Haematol. 1972 Mar;22(3):319-29
references.pmid: 4552217
references.citation: Toxicol Sci. 2004 Dec;82(2):647-55
references.pmid: 15456924
references.citation: Blood. 2000 Nov 1;96(9):2925-33
references.pmid: 11049968
references.citation: Biochemistry. 1985 Jan 1;24(1):34-9
references.pmid: 3994972
references.citation: Biochemistry. 1987 Mar 24;26(6):1777-83
references.pmid: 3593688
references.citation: Arch Biochem Biophys. 2005 Apr 1;436(1):121-7
references.pmid: 15752716
references.citation: Proc Natl Acad Sci U S A. 1986 May;83(10):3311-5
references.pmid: 3458184
references.citation: Blood. 1995 Sep 1;86(5):2014-20
references.pmid: 7655029
references.citation: J Lipid Res. 1965 Jul;6:428-31
references.pmid: 14336214
references.citation: Trans R Soc Trop Med Hyg. 1967;61(5):701-5
references.pmid: 6055561
references.citation: Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4
references.pmid: 388439
references.citation: Free Radic Biol Med. 2005 May 1;38(9):1257-64
references.pmid: 15808423
references.citation: J Biol Chem. 1951 Nov;193(1):265-75
references.pmid: 14907713
references.citation: Blood. 1997 Feb 15;89(4):1121-32
references.pmid: 9028933
references.citation: J Clin Invest. 1986 Nov;78(5):1155-60
references.pmid: 2945831
references.citation: J Biol Chem. 1960 Mar;235:769-75
references.pmid: 13793161
references.citation: Ann Hematol. 2001 Jan;80(1):32-7
references.pmid: 11233773
references.citation: Nature. 1970 Aug 15;227(5259):680-5
references.pmid: 5432063
references.citation: Arch Dermatol. 1984 Dec;120(12):1582-4
references.pmid: 6508329
references.citation: J Clin Invest. 1974 Sep;54(3):678-89
references.pmid: 4854449
references.citation: Blood. 1955 Jun;10(6):646-9
references.pmid: 14378284
references.citation: Mol Cell Biochem. 1995 May 24;146(2):99-105
references.pmid: 7565650
references.citation: J Biol Chem. 1988 Sep 25;263(27):13766-73
references.pmid: 2971044
references.citation: Biochim Biophys Acta. 1975 Jun 26;393(2):404-18
references.pmid: 167836
references.citation: Biochem J. 1964 Feb;90(2):374-8
references.pmid: 4284220
references.citation: Blood. 1984 Sep;64(3):733-41
references.pmid: 6466875
references.citation: Free Radic Res. 2004 May;38(5):527-34
references.pmid: 15293561
references.citation: Mol Biochem Parasitol. 2005 Jul;142(1):98-105
references.pmid: 15907563
references.citation: J Biol Chem. 1972 Nov 10;247(21):6960-2
references.pmid: 4673289
references.citation: J Biol Chem. 1991 Dec 15;266(35):23611-7
references.pmid: 1748639
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2402-7
references.pmid: 15701694
references.citation: Blood. 1948 Mar;3(3):249-75
references.pmid: 18902574
references.citation: J Biol Chem. 1984 Aug 25;259(16):10238-46
references.pmid: 6469962
references.citation: Blood. 1993 Jun 1;81(11):3146-52
references.pmid: 8499648
references.citation: Blood. 1987 Feb;69(2):401-7
references.pmid: 3542079
references.citation: Proc Natl Acad Sci U S A. 1987 Nov;84(21):7368-72
references.pmid: 3313392
references.citation: Arch Biochem Biophys. 1963 Jan;100:119-30
references.pmid: 14028302
references.citation: Mol Biochem Parasitol. 1983 Sep;9(1):15-28
references.pmid: 6199667
references.citation: Methods Enzymol. 1972;25:457-64
references.pmid: 23014426
references.citation: Science. 1985 Feb 1;227(4686):531-3
references.pmid: 2578228