Comparative analysis of pathologic processes developing in mice housed in SPF vs non-SPF conditions and treated with cyclophosphamide and dsDNA preparation.

Autor: Dolgova EV; Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090, Russia. Electronic address: dolgova.ev@mail.ru., Efremov YR; Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090, Russia., Taranov OS; The State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk Region 630559, Russia., Potter EA; Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090, Russia., Nikolin VP; Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090, Russia., Popova NA; Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090, Russia; Novosibirsk State University, Novosibirsk 630090, Russia., Omigov VV; The State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk Region 630559, Russia., Chernykh ER; Institute of Clinical Immunology, Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk 630099, Russia., Proskurina AS; Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090, Russia., Bogachev SS; Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090, Russia.
Jazyk: angličtina
Zdroj: Pathology, research and practice [Pathol Res Pract] 2015 Oct; Vol. 211 (10), pp. 754-8. Date of Electronic Publication: 2015 Jul 06.
DOI: 10.1016/j.prp.2015.07.002
Abstrakt: 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.
(Copyright © 2015 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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