EFFECTS OF PENTOXIFYLLINE ON THE ADHERENCE OF POLYMORPHONUCLEAR NEUTROPHILS TO OXIDANT-STIMULATED HUMAN ENDOTHELIAL-CELLS - INVOLVEMENT OF CYCLIC-AMP

Cultured human umbilical vein endothelial cells (HUVECs) treated with reactive oxygen species (ROS) show increased adherence of polymorphonu clear leukocytes (PMNs). Because pentoxifylline (PTX) is known to inhi bit cell interactions, we studied PMN adherence to ROS-stimulated HUVE Cs pretreated with PTX. ROS were generated by the oxidation of hypoxan thine by xanthine oxidase, giving rise to superoxide anion and hydroge n peroxide. Human PMNs were then added to HUVEC monolayers. After vari ous times, the cultures were washed and the number of adherent PMNs wa s estimated by measuring myeloperoxidase in the total cell homogenate. PTX inhibited adherence in a concentration dependent manner. Moreover , the increase in intracellular cAMP content varied with the PTX conce ntration. Isobutylmethylxanthine (IBMX) and isoproterenol (ISO), which increase intracellular cAMP content, also inhibited the adherence of PMNs to ROS-stimulated HUVECs. We conclude that cAMP is probably invol ved in the intracellular regulation of ROS-mediated PMN adherence to e ndothelial cells.