Targeted lipidomics yields changes in both arachidonic acid and linoleic acid pathways observed in C57BL/6J mice compared to KitW-sh mice after nitrogen mustard exposure

Sulfur mustard (SM) has been widely used as a chemical warfare agent
including most recently in Syria. Mice exposed to SM exhibit an
increase in pro-inflammatory cytokines followed by
immune cell infiltration in the lung, however, the mechanisms leading to
these inflammatory responses has not been completely elucidated. Mast
cells are one of the first responding innate immune cells found at the
mucosal surfaces of the lung and have been reported to be activated by SM
in the skin. Therefore, we hypothesized that nitrogen mustard (NM: a
surrogate for SM) exposure promotes activation of mast cells causing
chronic respiratory inflammation. To assess the role of mast cells
in NM-mediated pulmonary toxicity, we compared the
effects of NM exposure between C57BL/6
and B6.Cg-KitW-sh/HNihrJaeBsmJ (KitW-sh; mast cell
deficient) mice. Lung injury was observed in C57BL/6J mice following NM
exposure (0.125 mg/kg) at 72 h, which was significantly abrogated in
KitW-sh mice. Although both strains exhibited damage from NM,
C57BL/6J mice had higher inflammatory cell infiltration and more elevated
prostaglandin D2 (PGD2) present in bronchoalveolar lavage fluid
compared with KitW-sh mice. Additionally, we utilized murine
bone marrow-derived mast cells to
assess NM-inducedearly and late activation. Although NM exposure
did not result in mast cell degranulation, we observed an upregulation in
PGD2 and IL-6 levels following exposure to NM.
Results suggest that mast cells play a prominent role in lung injury
induced by NM and may contribute to the acute and
potentially long-term lung injury observed caused by SM.