Abstract 21312: Lactate Dehydrogenase A Affects Neutrophil Transcellular Extravasation by Upregulating Invadopodia Signaling

During inflammation, such as ischemia reperfusion injury or atherosclerosis, excessive neutrophil infiltration drives pathogenesis. Yet, the relationship between neutrophil transmigration and inflammation is ill-defined. Neutrophils migrate through endothelial cells (EC) via para (between EC) and transcellular (through an EC, TCM) mechanisms. During TCM, neutrophils interact with EC via invadopodia-like structures to form a ‘pore’ into EC membrane, thus facilitating neutrophil migration through EC body. We recently reported that deficiency in Rap1b, a member of RasGTPase superfamily, enhanced neutrophil recruitment to inflamed lungs and susceptibility to endotoxin shock. Rap1b-/- neutrophils exhibit increased TCM, invadopodia-like formation and metalloproteinase (MMP) release, suggesting mode of migration may influence inflammation outcome. Here, we used Rap1b-/- neutrophils to further investigate the link between neutrophil migration and inflammation. Using mass spectrometry, we found 2-fold increase in ...