The Roles of Cytoskeletal Regulating Proteins on the Modulation of Cortical Actin and the Impact on Neutrophil Deformation and Transit through Model Pulmonary Capillary Constrictions

Neutrophils are vital for host defense, but dysregulation in the pulmonary microvessels can cause acute lung injury and lead to respiratory distress syndrome. Understanding neutrophil trafficking is critical developing effective immunomodulatory therapies treat these pathologies. Neutrophil unique due diameter of capillaries (5μM) being smaller than neutrophils (8μM). This disparity results having deform pass through capillaries. Additionally, exposed chemical stimuli develop cortical actin stiffen, resulting even greater retention. To investigate biochemistry stiffening, we use conditionally immortalized progenitors that be genetically manipulated then differentiated into bona fide neutrophils. quantify effects f-MLP GM-CSF on stiffness nonadherent neutrophils, a microfluidic platform measure transit times 5μm constrictions. The dimensions force parameters were chosen mimic those capillary system. Our preliminary show addition slows rate transit, hazard ratio 0.7943 [95% CI 0.7135 0.8]) compared unstimulated control. has similar impact with 0.8070 0.7042 0.9248]). most dramatic effect was combining 0.5523 0.4799 0.6357]). Ultimately, interested proteins known regulate cytoskeletal organization. Early no longer induces faster rates vinculin-/- neutrophils; (∼ 1.109) HS1-/- (hematopoietic lineage cell-specific protein 1) (∼hazard 1.412).