Diabetic Bone Marrow Cell Injection Accelerated Acute Pancreatitis Progression

Abstract

Acute pancreatitis (AP) is one of the leading causes of hospital admission, 20% of which could progress to the severe type with extensive acinar cell necrosis. Clinical studies have reported that diabetes is an independent risk factor of the incidence of AP and is associated with higher severity than nondiabetic subjects. However, how diabetes participates in AP progression is not well defined. To investigate this question, wild-type (wt) and diabetic db/db mice at the age of 16 weeks were used in the study. AP was induced in wt recipients by 10 injections of 50 μg/kg caerulein with a 1 h interval. One hour after the last caerulein injection, bone marrow cells (BMC) isolated from wt and db/db mice were injected intraperitoneally into the recipients ( 1 × 10 7 cells/recipient). The recipients with no BMC injection served as controls. Thirteen hours after BMC injection, serum lipase activity was 1.8- and 1.3-folds higher in mice that received db/db BMC, compared with those with no injection and wt BMC injection, respectively ( p ≤ 0.02 for both). By H&E staining, the overall severity score was 14.7 for no cell injection and 16.6 for wt BMC injection and increased to 22.6 for db/db BMC injection ( p ≤ 0.002 for both). In particular, mice with db/db BMC injection developed more acinar cell necrosis and vacuolization than the other groups ( p ≤ 0.03 for both). When sections were stained with an antibody against myeloperoxidase (MPO), the density of MPO+ cells in pancreatitis was 1.9- and 1.6-folds higher than wt BMC and no BMC injection groups, separately ( p ≤ 0.02 for both). Quantified by ELISA, db/db BMC produced more IL-6, GM-CSF, and IL-10 compared with wt BMC ( p ≤ 0.04 for all). In conclusion, BMC of db/db mice produced more inflammatory cytokines. In response to acinar cell injury, diabetic BMC aggravated the inflammation cascade and acinar cell injury, leading to the progression of acute pancreatitis.

The purine metabolite inosine monophosphate accelerates myelopoiesis and acute pancreatitis progression

“…Previously, we showed that injection of BMCs from db/db mice into recipients with caerulein-induced AP resulted in more severe damage than injection of WT BMCs 12 . In this study, we used the same AP model to further compare the disease severity after injection of BMCs isolated from db/db mice at different ages.…”

“…To induce AP, C57BL/6 mice received ten intraperitoneal injections of 50 μg/kg caerulein at 1-hour intervals (Cae, AnaSpec, Inc. San Jose, CA, USA), as previously described 12 . Mice received the same number of PBS injection served as negative controls.…”

“…The enzymatic activity of ADSS and IMPDH2 in lineage −/low cells were also determined by ELISA, in accordance with the manufacturer’s instructions (MLBio, Shanghai, China). Plasma lipase and amylase activities were measured using commercial kits and quantified by a Tecan Safire microplate reader as previously described 12 . Plasma levels of myeloperoxidase (MPO) were determined using a Mouse MPO ELISA Kit (Abcam, Shanghai, China).…”

The impact of pulmonary tuberculosis on immunological and metabolic features of diabetic patients

“…Accumulating evidence suggests that immune cells are the main driver of metabolic disorders and inflammation, leading to adverse vascular outcomes. Data from patients and mice with diabetes have consistently demonstrated an increased ratio of myeloid cells to lymphocytes, which further increases with disease progression ( 11 , 12 ). In addition, intracellular levels of GM-CSF and IL-6 were higher in the bone marrow cells of db/db mice than in age-matched wild-type controls ( 12 ), indicating the pathological basis of skewed myelopoiesis.…”

“…Data from patients and mice with diabetes have consistently demonstrated an increased ratio of myeloid cells to lymphocytes, which further increases with disease progression ( 11 , 12 ). In addition, intracellular levels of GM-CSF and IL-6 were higher in the bone marrow cells of db/db mice than in age-matched wild-type controls ( 12 ), indicating the pathological basis of skewed myelopoiesis. In line with this, under sustained inflammatory conditions, infiltrating macrophages produce cytokines, such as IL-1β which promotes β cell dysfunction ( 13 ).…”