医学
口腔1
情感(语言学)
胰腺炎
钙
钙通道
髓系细胞
急性胰腺炎
髓样
内科学
电压依赖性钙通道
语言学
哲学
作者
Wentong Mei,Xiuli Zhang,Mengya Niu,Liang Li,Xiaoyu Guo,Gang Wang,Stephen J. Pandol,Li Wen,Feng Cao
标识
DOI:10.1016/j.pan.2024.04.001
摘要
Store-operated Ca2+ entry (SOCE) mediated by ORAI1 channel plays a crucial role in acute pancreatitis (AP). Macrophage is an important regulator in amplifying pancreatic tissue damage, but little is known about the role of ORAI1 in macrophages. In this study, we examined the effects of macrophage-specific ORAI1 on pancreatic tissue damage in AP. Myeloid-specific Orai1 deficient mice was generated by crossing a LysM-Cre mouse line with Orai1f/f mice. Bone marrow-derived macrophages (BMDMs) were isolated, cultured, and stimulated to induce M1 or M2 macrophage polarization. Intracellular Ca2+ signals were measured by time-lapse confocal microscope imaging, with a Ca2+ indicator (Fluo 4). Experimental AP was induced by hourly intraperitoneal injections of caerulein or retrograde biliopancreatic infusion of sodium taurocholate. Pancreatic tissue damage was assessed by histopathological scoring and immunostaining. Sepsis was induced by intraperitoneal injection of lipopolysaccharide; organ damage and serum pro-inflammatory cytokines were measured. Myeloid-specific Orai1 deletion exhibited minimal effect on SOCE in M0 macrophages and promoted M2 macrophage polarization ex vivo. Myeloid-specific Orai1 deletion did not affect pancreatic tissue damage, nor neutrophil or macrophage infiltration in two models of AP. Similarly, myeloid-specific Orai1 deletion did not influence overall survival rate in a model of sepsis, nor lung, kidney, and liver damage; while serum pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1β were higher in Orai1ΔLysM mice, but were largely reduced in mice with Orai1 inhibitor. Our data suggest that ORAI1 may not be a predominant SOCE channel in macrophages and play a limited role in mediating pancreatic tissue damage in AP.
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