Leukocytes adherent to the surfaces of both vascular biomaterials and normal blood vessels experience blood flow induced shear stress. The goal of the reported studies was to investigate the effect of fluid flow on the morphology, phagocytic function and stress response induction in adherent immune cells. Shear approximating arterial, venous and intermediate levels were applied onto glass-adherent IC21 macrophages in a temperature-controlled parallel plate flow system. The results indicate that fluid flow induces a shear-dependent physiological stress response in adherent macrophages and that significant morphological changes accompany macrophage responses to shear stress. In addition, arterial flow conditions induce not only significant cell polarisation, but also enhanced phagocytic ingestion in glass-adherent IC21 macrophages. These findings suggest that blood flow induced shear stress may not only be consequent to adherent leukocyte activation, but may also be integral to the regulation of adherent leukocyte behaviour in vivo.

T cell activation occurs following the recognition of MHC II-antigen complexes on antigenpresenting cells (APCs) and in conjunction with binding of costimulatory moleclues such as B7. The heat shock response is characterized by the synthesis of heat shock proteins (Hsp) that can alter normal subcellular regulatory pathways in order to repair stress induced cellular damage. Because Hsps can also contribute to normal cell function, the present studies were initiated to determine whether heat shock could be adapted to alter APC function and thereby increase T cell responses to alloantigen. LB27.4, a B cell APC line, was exposed to hyperthermic or normal temperature conditions and cocultured with the D10.G4 helper T cell line. Our results indicate that heat shock can enhance the ability of APCs to activate T cell function. The costimulatory molecule, B7-2 is responsible, at least in part, for the enhancement of APC function. Increased function occurred concomitantly with synthesis of Hsps. Using a cell line-based model system, these studies suggest one mechanism of immune regulation based on the physiological response to stress, and describe an engineering strategy whereby cellular function can be manipulated by the adaptation of the stress response.