Cellular specificity related to monoglyceride-induced cell death.
We have recently observed that monoglycerides (MGs), a family of lipids consisting of a single fatty acid moiety attached to a glycerol backbone, induce rapid dose-dependent apoptosis in murine thymocytes. In this work, we evaluated the sensitivity of various normal and malignant immune and non-immune cells to MGs. We demonstrate that the propensity to MG-induced death displayed by both T and B lymphocytes is clearly modulated according to their differentiation and activation status. For instance, the earliest T and B cell precursors are refractory to MG-mediated cell death. In the T-cell lineage, immature thymocytes are the most susceptible to MG treatment, while B cells from peripheral lymphoid organs appear more sensitive than B-cell subsets from the bone marrow. On the other hand, both activated T and B cells are more resistant to MG exposure than their non-activated counterparts. In addition, other hematopoietic lineages such as natural killer cells, macrophages, and erythroid cells are quite resistant to MG-induced death. Furthermore, using various immortalized cell lines from different tissues, we found that lymphomas and thymomas are the most sensitive among all lineages tested, while epithelial cells and fibroblasts are unaffected by MG treatment. Finally, MG-induced death was shown to be independent of Fas/Fas ligand (FasL) interactions. Altogether, our findings indicate that there is a cellular specificity related to MG-mediated cell death biased towards T and B lymphocytes. This suggests that MGs could potentially be used in the treatment of specific lymphoid disorders by bypassing the requirement for the Fas/FasL system.
Philippoussis
Fabianne
F
PROCREA BioSciences Inc., Division of Research & Development, 6100 Royalmount, Montreal, Quebec, Canada H4P 2R2.
Arguin
Chantal
C
Fortin
Marylène
M
Steff
Ann Muriel
AM
Hugo
Patrice
P
D016475:3T3 Cells / Q000473:pathology; D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000187:drug effects; D053222:Fas Ligand Protein; D005347:Fibroblasts / Q000187:drug effects; D005434:Flow Cytometry; D005989:Glycerides / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013945:Thymoma / Q000473:pathology; D014407:Tumor Cells, Cultured
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D005989:Glycerides; D008562:Membrane Glycoproteins