title: Comparative analysis of pathologic processes developing in mice housed in SPF vs non-SPF conditions and treated with cyclophosphamide and dsDNA preparation.
abstract: In our earlier studies, we observed that when mice are treated with cyclophosphamide and fragmented exogenous dsDNA (18-30 h post cytostatic treatment), they develop a very characteristic set of symptoms and 80-90% of such animals succumb within 6-25 days. This was called "delayed death" phenomenon, and the gap between cyclophosphamide and DNA injections required for such phenotype to develop was termed "death window". We established that mice succumbed to multi-organ failure, which was caused by systemic inflammation and sepsis. These processes unfolded along with accidental involution of lymphoid organs, which resulted from the failure of CD34(+) hematopoietic stem cells to differentiate into lymphoid lineage progenitors. Here we compare SPF and non-SPF animals, and demonstrate that the major cause of systemic inflammation and sepsis observed upon such treatments is activation of an opportunistic infection. Mice of the same strain (CBA) housed under SPF conditions do not develop the characteristic symptoms, nor do they become moribund. Yet, regardless of the breeding conditions, upon synergistic action of cyclophosphamide and dsDNA, CD34(+) hematopoietic stem cells consistently fail to give rise to lymphoid lineage progenitors. We demonstrate that this differentiation defect is reversible and that population of lymphoid progenitors is restored by day 29 after cyclophosphamide injection.
authors: Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090, Russia. Electronic address: dolgova.ev@mail.ru.
authors: Evgeniya V
authors: EV
authors: Dolgova
authors: Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090, Russia.
authors: Yaroslav R
authors: YR
authors: Efremov
authors: The State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk Region 630559, Russia.
authors: Oleg S
authors: OS
authors: Taranov
authors: Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090, Russia.
authors: Ekaterina A
authors: EA
authors: Potter
authors: Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090, Russia.
authors: Valeriy P
authors: VP
authors: Nikolin
authors: Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090, Russia; Novosibirsk State University, Novosibirsk 630090, Russia.
authors: Nelly A
authors: NA
authors: Popova
authors: The State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk Region 630559, Russia.
authors: Vladimir V
authors: VV
authors: Omigov
authors: Institute of Clinical Immunology, Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk 630099, Russia.
authors: Elena R
authors: ER
authors: Chernykh
authors: Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090, Russia.
authors: Anastasia S
authors: AS
authors: Proskurina
authors: Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090, Russia.
authors: Sergey S
authors: SS
authors: Bogachev
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D008808:Mice, Inbred CBA
chemical_list: D003520:Cyclophosphamide; D004247:DNA
keywords: Double-stranded DNA; Lymphoid progenitors; Opportunistic infection; SPF mice; Systemic inflammation