More Than A Movement: Unpacking Contemporary Anti-Human Trafficking Efforts in Washington, D.C.

Trafficking in persons has attracted seemingly boundless attention over the last two decades and the work aimed at fighting it is best understood when this cause is contextualized against the backdrop of other social forces—economic, social, and cultural—shaping contemporary nonprofit activities. This project argues that the paid and volunteer labor that takes place in metro Washington, D.C., to combat trafficking in persons can be understood as both a movement and an industry. In addition to arguing that anti-trafficking work is part of a nonprofit industrial complex that situates activist and advocacy work firmly inside state and economic institutions, this project is concerned with the ways in which trafficking work and workers conduct their business collectively. As an organizational study, it identifies the key players in the D.C. region focused on this issue and traces their interactions, collaborations, and cooperation. Significantly, this project suggests that despite variations in objectives, methods, priorities, and characterizations of trafficking, thirty organizations in metro D.C. working on this issue “get along” because they are bound by the benign common goal of raising awareness. Awareness, in this context, is best understood as both a cultural anchor facilitating cohesion and as a social currency allowing groups to opt into joint efforts. The dissertation concludes that organizations centralize awareness in their collective activities over more drastic priorities around which consensus would need to be gained. This is a lost opportunity for making sense of the ways that individual bodies—men, women, and children—experience not just trafficking, but the world around them.

ROLE OF ICAM-1-MEDIATED ENDOCYTOSIS IN ENDOTHELIAL FUNCTION AND IMPLICATIONS FOR CARRIER-ASSISTED DRUG DELIVERY

Intercellular adhesion molecule 1 (ICAM-1) is a transmembrane protein found on the surface of vascular endothelial cells (ECs). Its expression is upregulated at inflammatory sites, allowing for targeted delivery of therapeutics using ICAM-1-binding drug carriers. Engagement of multiple copies of ICAM-1 by these drug carriers induces cell adhesion molecule (CAM)-mediated endocytosis, which results in trafficking of carriers to lysosomes and across ECs. Knowledge about the regulation behind CAM-mediated endocytosis can help improve drug delivery, but questions remain about these regulatory mechanisms. Furthermore, little is known about the natural function of this endocytic pathway. To address these gaps in knowledge, we focused on two natural binding partners of ICAM-1 that potentially elicit CAM-mediated endocytosis: leukocytes (which bind ICAM-1 via β₂ integrins) and fibrin polymers (a main component of blood clots which binds ICAM-1 via the γ3 sequence). First, inspired by properties of these natural binding partners, we varied the size and targeting moiety of model drug carriers to determine how these parameters affect CAM-mediated endocytosis. Increasing ICAM-1-targeted carrier size slowed carrier uptake kinetics, reduced carrier trafficking to lysosomes, and increased carrier transport across ECs. Changing targeting moieties from antibodies to peptides decreased particle binding and uptake, lowered trafficking to lysosomes, and increased transport across ECs. Second, using cell culture models of leukocyte/EC interactions, inhibiting regulatory elements of the CAM-mediated pathway disrupted leukocyte sampling, a process crucial to leukocyte crossing of endothelial layers (transmigration). This inhibition also decreased leukocyte transmigration across ECs, specifically through the transcellular route, which occurs through a single EC without disassembly of cell-cell junctions. Third, fibrin meshes, which mimic blood clot fragments/remnants, bound to ECs at ICAM-1-enriched sites and were internalized by the endothelium. Inhibiting the CAM-mediated pathway disrupted this uptake. Following endocytosis, fibrin meshes trafficked to lysosomes where they were degraded. In mouse models, CAM-mediated endocytosis of fibrin meshes appeared to remove fibrin remnants at the endothelial surface, preventing re-initiation of the coagulation cascade. Overall, these results support a link between CAM-mediated endocytosis and leukocyte transmigration as well as uptake of fibrin materials by ECs. Furthermore, these results will guide the future design of ICAM-1-targeted carrier-assisted therapies.