Synthetic exogenous lysophosphatidylcholine (LPC) was used to induce leukocyte-endothelial cell interaction, utilizing intravital microscopy in the rat mesenteric microvasculature. Superfusion of the rat mesentery with 10 microM LPC significantly and time dependently increased leukocyte rolling and adherence compared with control rats. Moreover, LPC superfusion did not alter systemic blood pressure or mesenteric venular shear rate. Administration of either an anti-P-selectin monoclonal antibody (PB1.3 at 1 mg/kg i.v.) or a nitric oxide (NO) donor (CAS-1609, 10 microM superfusion) markedly attenuated LPC-induced leukocyte rolling and adherence (P < 0.01 from LPC alone). Immunohistochemical localization of P-selectin and intercellular adhesion molecule-1 (ICAM-1) expression on mesenteric venules was significantly increased after exposure to LPC compared with mesenteries superfused with phosphatidylcholine (P < 0.001). Flow cytometric analysis indicated that 10 microM LPC significantly (P < 0.05) increased P-selectin fluorescence on rat platelets. Furthermore, direct measurement of NO release from rat aortic vascular endothelium was significantly (P < 0.05) inhibited by 10 microM LPC. Thus LPC induces in vivo leukocyte rolling and adherence in the mesenteric rat microvasculature by increasing the surface expression of P-selectin and ICAM-1. Because inhibition of endothelial NO release promotes P-selectin expression, LPC-induced rolling and adherence may be mediated via reduced NO release.