In the event of a radiologic catastrophe, endothelial cell and neutrophil dysfunction play important roles<br>in tissue injury.Clinically available therapeutics for radiation-induced vascular injury are largely supportive. PKCd<br>was identified as a critical regulator of the inflammatory response, and its inhibition was shown to protect critical<br>organs during sepsis. We used a novel biomimetic microfluidic assay (bMFA) to interrogate the role of PKCd in<br>radiation-induced neutrophil–endothelial cell interaction and endothelial cell function. HUVECs formed a complete<br>lumen in bMFA and were treated with 0.5, 2, or 5 Gy ionizing radiation (IR). At 24 h post-IR, the cells were<br>treatedwitha PKCd inhibitor for an additional 24h.Under physiologic shear flow, the role of PKCd on endothelium<br>function and neutrophil adherence/migration was determined. PKCd inhibition dramatically attenuated IRinduced<br>endothelium permeability increase and significantly decreased neutrophil migration across IR-treated<br>endothelial cells. Moreover, neutrophil adhesion to irradiated endothelial cells was significantly decreased after<br>PKCd inhibition in a flow-dependentmanner. PKCd inhibition downregulated IR-induced P-selectin, intercellular<br>adhesion molecule 1, and VCAM-1 but not E-selectin overexpression. PKCd is an important regulator of<br>neutrophil–endothelial cell interaction post-IR, and its inhibition can serve as a potential radiation medical<br>countermeasure.