Reduced tissue immigration of monocytes by neuropeptide Y during endotoxemia is associated with Y2 receptor activation

Abstract

Neuropeptide Y (NPY) increases survival in experimental septic shock, which might be mediated by cardiovascular and/or immunological effects. To study the latter hypothesis, we monitored blood leukocyte subsets over 96 h after intravenous (i.v.) application of LPS in chronically i.v.-cannulated rats. LPS induced a dramatic leukopenia at 4 h after challenge, which was blunted in NPY-treated animals by stabilizing granulocyte and T-lymphocyte numbers. In addition, NPY treatment prevented tissue immigration of monocytes at early time points and consecutively mobilized activated monocytes from the third day after challenge. RT-PCR and in vitro adhesion studies provided evidence for a NPY Y2 receptor-mediated effect on monocytes. Thus, NPY treatment has profound receptor-specific effects on the migration and adhesion of leukocytes under endotoxemic conditions.