Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes

Most migrating cells extrude their front by the force of actin polymerization. Polymerization requires an initial nucleation step, which is mediated by factors establishing either parallel filaments in the case of filopodia or branched filaments that form the branched lamellipodial network. Branches are considered essential for regular cell motility and are initiated by the Arp2/3 complex, which in turn is activated by nucleation-promoting factors of the WASP and WAVE families. Here we employed rapid amoeboid crawling leukocytes and found that deletion of the WAVE complex eliminated actin branching and thus lamellipodia formation. The cells were left with parallel filaments at the leading edge, which translated, depending on the differentiation status of the cell, into a unipolar pointed cell shape or cells with multiple filopodia. Remarkably, unipolar cells migrated with increased speed and enormous directional persistence, while they were unable to turn towards chemotactic gradients. Cells with multiple filopodia retained chemotactic activity but their migration was progressively impaired with increasing geometrical complexity of the extracellular environment. These findings establish that diversified leading edge protrusions serve as explorative structures while they slow down actual locomotion

Management and outcome of bleeding pseudoaneurysm associated with chronic pancreatitis

<p>Abstract</p> <p>Background</p> <p>A bleeding pseudoaneurysm in patients with chronic pancreatitis is a rare and potentially lethal complication. Optimal treatment of bleeding peripancreatic pseudoaneurysm remains controversial. This study reports on experience at Chang Gung Memorial Hospital (CGMH) in managing of bleeding pseudoaneurysms associated with chronic pancreatitis.</p> <p>Methods</p> <p>The medical records of 9 patients (8 males and 1 female; age range, 28 – 71 years; median, 36 years) with bleeding pseudoaneurysms associated with chronic pancreatitis treated at CGMH between Aug. 1992 and Sep. 2004 were retrospectively reviewed. Alcohol abuse (n = 7;78%) was the predominant predisposing factor. Diagnoses of bleeding pseudoaneurysms were based on angiographic (7/7), computed tomographic (4/7), ultrasound (2/5), and surgical (2/2) findings. Whether surgery or angiographic embolization was performed was primarily based on patient clinical condition. Median follow-up was 38 months (range, 4 – 87 months).</p> <p>Results</p> <p>Abdominal computed tomography revealed bleeding pseudoaneurysms in 4 of 7 patients (57%). Angiography determined correct diagnosis in 7 patients (7/7, 100%). The splenic artery was involved in 5 cases, the pancreaticoduodenal artery in 2, the gastroduodenal artery in 1, and the middle colic artery in 1. Initial treatment was emergency (n = 4) or elective (n = 3) surgery in 7 patients and arterial embolization in 2. Rebleeding was detected after initial treatment in 3 patients. Overall, 5 arterial embolizations and 9 surgical interventions were performed; the respective rates of success of these treatments were 20% (1/5) and 89% (8/9). Five patients developed pseudocysts before treatment (n = 3) or following intervention (n = 2). Pseudocyst formation was identified in 2 of the 3 rebleeding patients. Five patients underwent surgical treatment for associated pseudocysts and bleeding did not recur. One patient died from angiography-related complications. Overall mortality rate was 11% (1/9). Surgery-related mortality was 0%.</p> <p>Conclusion</p> <p>Angiography is valuable in localizing bleeding pseudoaneurysms. In this limited series, patients with bleeding pseudoaneurysms associated with chronic pancreatitis treated surgically seemingly obtained good outcomes.</p