Increased endothelial cell adhesion molecule (ECAM) expression, leukocyte-endothelial cell adhesive interactions (LECA), platelet-endothelial cell adhesion (PECA), mast cell activation, production of
reactive oxygen species (ROS), and microvascular permeability are hallmarks of the inflammatory response. The infiltration of inflammatory phagocytes is associated with
myeloperoxidase (MPO)-dependent production of
hypochlorous acid, a reactive chlorinating species that targets
membrane lipids to produce halogenated
lipids such as
2-chlorohexadecanal (2-ClHDA) and 2-chloropalmitic
acid (2-ClPA). Whether these chlorinated
lipids contribute to microcirculatory dysfunction is largely unknown. Thus, the objectives of this study were to determine if chlorinated
lipids exposure induces such inflammatory responses in an in vitro model employing cultured human intestinal mesenteric vascular endothelial cells (HIMVEC), and in an in vivo model examining responses in small intestinal and mesenteric postcapillary venules of naive rats. Following the addition of either 2-ClPA or 2-ClHDA to the culture medium, HIMVEC displayed increased platelet and neutrophil adherence that was associated with elevated expression of ECAMs and increased permeability. In vivo, chlorinated
lipid exposure significantly increased LECA, PECA, ROS production, and
albumin leakage, inflammatory events that were associated with mast cell activation and increased tissue MPO activity and expression. Our data provide proof-of-principle that 2-ClPA and 2-ClHDA induce powerful proinflammatory responses both in vitro and in vivo, suggesting the possibility that these chlorinated
lipid products of the MPO/
hydrogen peroxide /
chloride system may contribute to
inflammation noted in neutrophil-dependent,
myeloperoxidase-mediated pathologic states such as
ischemia/reperfusion,
hemorrhagic shock, and
sepsis.