Dataset Information

Mobilization of CD11b⁺/Ly6c^hi monocytes causes multi organ dysfunction syndrome in acute pancreatitis.

ABSTRACT:

Objective

Acute pancreatitis (AP) is an inflammatory disorder, the severe form of which is burdened with multi-organ dysfunction and high mortality. The pathogenesis of life -threatening organ complications, such as respiratory and renal failure, is unknown.

Design

Organ dysfunction was investigated in a mouse model of AP. The influence of monocytes and neutrophils on multi organ dysfunction syndrome (MODS) was investigated in vivo by antibody depletion. Using real-time-fluorescence and deformability-cytometry (RT-DC) analysis we determined the mechanical properties of neutrophils and monocytes during AP. Furthermore, blood samples of pancreatitis patients were used to characterize severity-dependent chemokine profiles according to the revised Atlanta classification.

Results

Similar to AP in humans, severe disease in the mouse model associates with organ dysfunction mainly of lung and kidney, which is triggered by a mobilisation of Ly6g^-/CD11b⁺/Ly6c ^hi monocytes, but not of Ly6g⁺/CD11b⁺ neutrophils. Monocyte depletion by anti-CCR2 antibody treatment ameliorated lung function (oxygen consumption) without interfering with the systemic immune response. RT-DC analysis of circulation monocytes showed a significant increase in cell size during SAP, but without a compensatory increase in elasticity. Patient chemokine profiles show a correlation of AP severity with monocyte attracting chemokines like MCP-1 or MIG and with leukocyte mobilisation.

Conclusion

In AP, the physical properties of mobilized monocytes, especially their large size, result in an obstruction of the fine capillary systems of the lung and of the kidney glomeruli. A selective depletion of monocytes may represent a treatment strategy for pancreatitis as well as for other inflammation-related disorders.

SUBMITTER: Wilden A

PROVIDER: S-EPMC9589437 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mobilization of CD11b<sup>+</sup>/Ly6c<sup>hi</sup> monocytes causes multi organ dysfunction syndrome in acute pancreatitis.

Wilden Anika A Glaubitz Juliane J Otto Oliver O Biedenweg Doreen D Nauck Matthias M Mack Matthias M Ribback Silvia S Bröker Barbara M BM von Rheinbaben Sabrina Freiin SF Lerch Markus M MM Aghdassi Ali Alexander AA Weiss Frank Ulrich FU Sendler Matthias M

Frontiers in immunology 20221010

<h4>Objective</h4>Acute pancreatitis (AP) is an inflammatory disorder, the severe form of which is burdened with multi-organ dysfunction and high mortality. The pathogenesis of life -threatening organ complications, such as respiratory and renal failure, is unknown.<h4>Design</h4>Organ dysfunction was investigated in a mouse model of AP. The influence of monocytes and neutrophils on multi organ dysfunction syndrome (MODS) was investigated <i>in vivo</i> by antibody depletion. Using real-time-flu ...[more]

PMID: 36300116

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Project description:Heme oxygenase-1 (Hmox1) is a stress-inducible protein crucial in heme catabolism. The end products of its enzymatic activity possess anti-oxidative, anti-apoptotic and anti-inflammatory properties. Cardioprotective effects of Hmox1 were demonstrated in experimental models of myocardial infarction (MI). Nevertheless, its importance in timely resolution of post-ischemic inflammation remains incompletely understood. The aim of this study was to determine the role of Hmox1 in the monocyte/macrophage-mediated cardiac remodeling in a mouse model of MI. Hmox1 knockout (Hmox1-/-) and wild-type (WT, Hmox1+/+) mice were subjected to a permanent ligation of the left anterior descending coronary artery. Significantly lower incidence of left ventricle (LV) free wall rupture was noted between 3rd and 5th day after MI in Hmox1-/- mice resulting in their better overall survival. Then, starting from 7th until 21st day post-MI a more potent deterioration of LV function was observed in Hmox1-/- than in the surviving Hmox1+/+ mice. This was accompanied by higher numbers of Ly6Chi monocytes in peripheral blood, as well as higher expression of monocyte chemoattractant protein-1 and adhesion molecules in the hearts of MI-operated Hmox1-/- mice. Consequently, a greater post-MI monocyte-derived myocardial macrophage infiltration was noted in Hmox1-deficient individuals. Splenectomy decreased the numbers of circulating inflammatory Ly6Chi monocytes in blood, reduced the numbers of proinflammatory cardiac macrophages and significantly improved the post-MI LV function in Hmox1-/- mice. In conclusion, Hmox1 deficiency has divergent consequences in MI. On the one hand, it improves early post-MI survival by decreasing the occurrence of cardiac rupture. Afterwards, however, the hearts of Hmox1-deficient mice undergo adverse late LV remodeling due to overactive and prolonged post-ischemic inflammatory response. We identified spleen as an important source of these cardiovascular complications in Hmox1-/- mice.

Dataset Information

Mobilization of CD11b⁺/Ly6c^hi monocytes causes multi organ dysfunction syndrome in acute pancreatitis.

Objective

Design

Results

Conclusion

Publications

Mobilization of CD11b<sup>+</sup>/Ly6c<sup>hi</sup> monocytes causes multi organ dysfunction syndrome in acute pancreatitis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Mobilization of CD11b+/Ly6chi monocytes causes multi organ dysfunction syndrome in acute pancreatitis.

Objective

Design

Results

Conclusion

Publications

Mobilization of CD11b<sup>+</sup>/Ly6c<sup>hi</sup> monocytes causes multi organ dysfunction syndrome in acute pancreatitis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Mobilization of CD11b⁺/Ly6c^hi monocytes causes multi organ dysfunction syndrome in acute pancreatitis.