Reverse-migrated neutrophils regulated by JAM-C are involved in acute pancreatitis-associated lung injury

Abstract

Junctional adhesion molecule-C (JAM-C) plays a key role in the promotion of the reverse transendothelial migration (rTEM) of neutrophils, which contributes to the dissemination of systemic inflammation and to secondary organ damage. During acute pancreatitis (AP), systemic inflammatory responses lead to distant organ damage and typically result in acute lung injury (ALI). Here, we investigated the role of rTEM neutrophils in AP-associated ALI and the molecular mechanisms by which JAM-C regulates neutrophil rTEM in this disorder. In this study, rTEM neutrophils were identified in the peripheral blood both in murine model of AP and human patients with AP, which elevated with increased severity of lung injury. Pancreatic JAM-C was downregulated during murine experimental pancreatitis, whose expression levels were inversely correlated with both increased neutrophil rTEM and severity of lung injury. Knockout of JAM-C resulted in more severe lung injury and systemic inflammation. Significantly greater numbers of rTEM neutrophils were present both in the circulation and pulmonary vascular washout in JAM-C knockout mice with AP. This study demonstrates that during AP, neutrophils that are recruited to the pancreas may migrate back into the circulation and then contribute to ALI. JAM-C downregulation may contribute to AP-associated ALI via promoting neutrophil rTEM.

Eff ects of hemin, a heme oxygenase-1 inducer in L-arginine-induced acute pancreatitis and associated lung injury in adult male albino rats

“…Lung injury results from the local pulmonary endothelial cell injury resulted from the neutrophil-generated oxygen-radical products. Finally, pancreatitis-associated ALI is further related to specifi c eff ects on pancreatic enzymes like proteases and phospholipase A 2 (Wu et al 2016).…”

Dachengqi Decoction Attenuates Intestinal Vascular Endothelial Injury in Severe Acute Pancreatitis in Vitro and in Vivo

“…We observed changes in permeability and apoptosis rates in endothelial cells. Since AQP-1, MMP9, and JAM-C all play key roles in regulating capillary permeability in SAP [9-11], we also observed changes in the expression of endothelial barrier function-related proteins such as AQP-1, MMP-9, and JAM-C proteins and mRNA. We found that after adding TNF-α (10 ng/mL), the TEER permeability measurements and apoptosis rates of the endothelial cells increased at 6 h, 12 h, and 24 h. These results are consistent with the results of our previous study [22].…”

“…Aquaporins (AQPs), matrix metalloproteinases (MMPs), and junctional adhesion molecules (JAMs) are important structural proteins of these parts, respectively. Studies showed that aquaporin 1 (AQP-1), matrix metalloproteinase 9 (MMP9), and junctional adhesion molecule-C (JAM-C) all play key roles in regulating capillary permeability in SAP [9-11]. AQP-1 is crucial to the translocation and balance of water both inside and outside the cells and blood vessels.…”

Chronic Pancreatitis Associated Acute Respiratory Failure

“…A very recent report indicates that during AP, neutrophils that are recruited to the pancreas may reverse migrate back into the circulation and further contribute to ALI. These reverse migrated neutrophils during ALI are regulated by Junctional adhesion molecule-C (JAM-C), and this process is termed reverse trans-endothelial migration (rTEM) of neutrophils [20]. Another interesting report examined the process that neutrophils use to eliminate invading microorganisms by expelling nuclear DNA and histones to form extracellular web-like structures called neutrophil extracellular traps (NETs).…”