Effect of soman poisoning on populations of bone marrow and peripheral blood cells in mice.
According to recent reports, brain lesions resulting from ischemia, mechanical injury or neurodegenerative diseases can be partially treated using bone marrow-derived stromal cell (BMSC) engraftment approaches. Nevertheless, for brain lesions resulting from organophosphate poisoning, nerve agents such as soman (pinacolyl methylphosphono-fluoridate) could affect blood and bone marrow (BM) micro-environments, thus preventing efficient BMSC migration and engraftment. It is therefore necessary to verify the hematologic response to soman exposure. To assess this issue, the survival of BM cells, in particular hematopoietic progenitor and precursor cells (HPC), as well as distribution of the different populations of peripheral blood cells, were investigated in soman-intoxicated mice. Nine-week-old adult male B6D2F1 mice were treated with 110 microg/kg soman and 5.0 mg/kg methyl nitrate atropine. BM and peripheral blood (PB) samples were collected 1, 4, 8 and 22 days after poisoning. Various parameters were determined such as PB cell counting or, for BM samples, myelogram, in vitro colony-forming cells and phenotypic flow cytometry analysis. On post-soman day 1, a significant decrease in numbers of white blood cells and an increase in erythrocyte and platelet counts were noted. On post-soman day 4, the number of HPC decreased significantly, probably due to reduction of the replication rate of these immature cells. However, the number of more immature cells (Sca1+/Lin- phenotype) remained unchanged. On post-soman day 8 and day 22, the number of monocytes and granulocytes in the blood had considerably increased, probably due to a strong inflammatory reaction in response to soman poisoning. In conclusion, PB cell and BM-derived HPC populations are affected by acute soman poisoning, suggesting particular care, mainly for graft kinetic aspects, during future development of autologous BM stem cell therapy strategy to treat nerve agent-induced brain damage.
Collombet
Jean-Marc
JM
Département de Toxicologie, CRSSA 24, Avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex, France. jmcollombet@crssa.net
Mourcin
Frédéric
F
Grenier
Nancy
N
Four
Elise
E
Masqueliez
Catherine
C
Baubichon
Dominique
D
Lallement
Guy
G
Hérodin
Francis
F
D000818:Animals; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology; D001973:Bromodeoxyuridine; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000506:poisoning*; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D009192:Myelography; D012999:Soman / Q000506:poisoning*; D013234:Stem Cells / Q000187:drug effects; D013997:Time Factors
D002619:Chemical Warfare Agents; D012999:Soman; D001973:Bromodeoxyuridine