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Bone marrow inflammation precedes hexahydro‐1‐nitroso‐3, 5‐ dinitro‐1, 3, 5‐triazine (MNX) induced delayed myelosuppression in rats.
Author(s) -
Jaligama Sridhar,
Kale Vijay M.,
Wilbanks Mitchell S.,
Perkins Edward J.,
Meyer Sharon A.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.888.5
Subject(s) - bone marrow , inflammation , endocrinology , medicine , myelopoiesis , chemokine , infiltration (hvac) , haematopoiesis , granulocyte , immunology , pharmacology , chemistry , biology , microbiology and biotechnology , thermodynamics , physics , stem cell
MNX, an environmental nitroreduced product of munitions RDX contaminates military sites. Our previous studies identified bone marrow (BM) as target of acute oral exposure to MNX in rats in the form of delayed loss of BM Granulocyte Macrophage Colony Forming Cells (GM‐CFCs) and concomitant decrease in blood granulocytes (NOAELs 24, 47 mg/kg resp) at 14 days after exposure. To address whether delayed effects of MNX are due to persistence of early hematological effects or are late‐onset due to required expression period, female Sprague‐Dawley rats were orally gavaged with MNX from 0 to 94 mg/kg and different toxicological endpoints were evaluated over a time course at 2, 7, 10, 12, and 14d. A significant increase in blood granulocytes and circulating levels of RANTES, a leukocyte chemokine, indicate that an acute inflammatory response occurs at 2d after exposure to MNX. Also, persistent BM macrophage infiltration in MNX (94 mg/kg) treated rat iliums (24h, 2d and 10d) and activation of NFkB signaling pathway in BM cells at 10d were observed. Further, increase in adherent BM mesenchymal stromal cell colonies constituting macrophages, endothelial cells and fibroblasts was observed in MNX treated rats. Collectively, these data suggest that myelosuppression is delayed until 10d presumably due to development of inhibitory effects of preceding BM inflammation on myelopoiesis. (Support: DoD/CDMRP, US Army Corps of Engineers)