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A novel nonphagocytic mechanism of erythrocyte destruction involving direct cell-mediated cytotoxicity.

Authors
Saxena-RK; Chandrasekhar-B
Source
Int J Hematol 2000 Apr; 71(3):227-237
NIOSHTIC No.
20032674
Abstract
The number of erythrocytes fell when co-cultured with cell preparations derived from mouse spleen, thymus, bone marrow, or peritoneal exudate (PE) cells. Erythrocyte-depletion activities (EDA) of different leukocyte preparations were in the order PE > spleen > thymus > bone marrow. Adherent, nonadherent, T-depleted, and T-enriched cell subpopulations had comparable EDA. Spleen cells from athymic nude mice, however, lacked significant EDA. In addition, EDA was boosted by Concanavalin A (Con A) but not by lipopolysaccharide, indicating that T cells may play a crucial role in inducing EDA in spleen cells. Paraformaldehyde-fixed spleen or PE cells, as well as membrane preparations isolated from spleen cells, efficiently lysed erythrocytes. Erythrocyte ghost membranes inhibited erythrocyte lysis by control or paraformaldehyde-fixed spleen cells. Treatment with hamster anti-mouse Fas or anti-mouse tumor necrosis factor receptor (TNFR) antibody could opsonize erythrocytes for faster depletion by spleen cells, suggesting an expression of Fas and TNFR on erythrocytes. TNF alpha could lyse erythrocytes in a dose-dependent fashion. Additionally, enhanced spleen cell EDA induced in response to succenyl Con-A could be blocked by anti-TNF alpha antibodies. Our results provide evidence for a direct cell-mediated cytotoxicity (CMC) of erythrocytes by leukocytes. A role of molecules of Fas and the TNF family in CMC of erythrocytes has also been suggested. Further work is needed to understand if, and to what extent, CMC of erythrocytes contributes to erythrocyte destruction in vivo and to determine its patho-physiological significance.
Keywords
Analytical-processes; Animal-studies; Cell-alteration; Cell-biology; Cell-function; Cell-metabolism; Cell-transformation; Cellular-reactions; Cell-damage
Contact
RK Saxena, NIOSH, ASB, 1095 Willowdale Rd, Morgantown, WV 26505
CODEN
IJHEEY
Publication Date
20000401
Document Type
Journal Article
Fiscal Year
2000
NTIS Accession No.
NTIS Price
Issue of Publication
3
ISSN
0925-5710
NIOSH Division
HELD
Source Name
International Journal of Hematology
State
WV
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