Methods for controlling and regulating engulfment, uptake and/or transcellular transport at a stage following initial engagement of an agent to the endothelium are provided, based on the identification of CAM-mediated endocytosis and the sphingomyelin/ceramide pathway as active steps in transcellular TEM. Administration of regulators relating to the identified pathways, such as NHE1, sphingomyelinases, acid sphingomyelinase and ceramide, permit control and regulation of uptake and transcellular transport. Control and regulation of uptake and/or transcellular transport is applicable in strategies to modulate inflammation, provide controlled and/or targeted delivery of agents, control pathogenic invasion, recover action of an inhibited CAM-mediated uptake or transendothelial pathway, or provide uptake or transendothelial transport by targeting cell surface markers other than ICAM-1.
