Extracellular Vesicle ITGAM and ITGB2 Mediate Severe Acute Pancreatitis-Related Acute Lung Injury

Abstract

Integrins expressed on extracellular vesicles (EVs) secreted by various cancers are reported to mediate the organotropism of these EVs. Our previous experiment found that pancreatic tissue of mice with severe cases of acute pancreatitis (SAP) overexpresses several integrins and that serum EVs of these mice (SAP-EVs) can mediate acute lung injury (ALI). It is unclear if SAP-EV express integrins that can promote their accumulation in the lung to promote ALI. Here, we report that SAP-EV overexpress several integrins and that preincubation of SAP-EV with the integrin antagonist peptide HYD-1 markedly attenuates their pulmonary inflammation and disrupt the pulmonary microvascular endothelial cell (PMVEC) barrier. Further, we report that injecting SAP mice with EVs engineered to overexpress two of these integrins (ITGAM and ITGB2) can attenuate the pulmonary accumulation of pancreas-derived EVs and similarly decrease pulmonary inflammation and disruption of the endothelial cell barrier. Based on these findings, we propose that pancreatic EVs can mediate ALI in SAP patients and that this injury response could be attenuated by administering EVs that overexpress ITGAM and/or ITGB2, which is worthy of further study due to the lack of effective therapies for SAP-induced ALI.

Regulation of Microtubule Stability in Pulmonary Microvascular Endothelial Cells in Rats with Severe Acute Pancreatitis: Qingyi Decoction is a Potential CDK5 Inhibitor

“…In addition, researchers have identified extracellular vesicle ITGAM and ITGB2 as being important in the pathogenesis of lung injury secondary to SAP. 34 In this study, STC retrograde biliopancreatic duct injection induced a stable and reliable model of pancreatic and lung injury in rats. QYD effectively alleviated SAP and SAP-related acute lung injuries, reduced inflammation and pulmonary edema, and restored their ventilatory function.…”

Urolithin A’s Role in Alleviating Severe Acute Pancreatitis via Endoplasmic Reticulum-Mitochondrial Calcium Channel Modulation

“…Pancreatic acinar cell injury is the origin of SAP inflammation. In our previous research, the pathogenic characteristics of EVs from the plasma of SAP mice (SAP-EVs) were confirmed, and these EVs were shown to more accurately simulate cell-to-cell communication and inflammation signaling in vivo conditions . Therefore, we used SAP-EVs to damage the isolated acinar cells and compared the protective effects of pomegranate-derived extracellular vesicles (P-EVs) and UA.…”

“…The sham group received no intervention. The SAP-EVs group was coincubated with SAP-EVs at a concentration of 20 μg/mL . In the UA group, 10 μg/μL UA was added based on the dosage established in supplementary studies (Figure S1), along with the same concentration of SAP-EVs.…”

Development and validation of a pyroptosis-related prognostic signature associated with osteosarcoma metastasis and immune infiltration

“…[ 16 ] ITGAM was identified as a serum exosomal protein marker of lung adenocarcinoma. [ 17 ] ITGAM might be strongly linked to the carcinogenesis and the development of anaplastic thyroid cancer. [ 18 ] The CCL2-CCR2 axis exerts 85 significant biological activities in dogs with metastatic OS.…”