Wilden, Anika and Glaubitz, Juliane and Otto, Oliver and Biedenweg, Doreen and Nauck, Matthias and Mack, Matthias and Ribback, Silvia and Broeker, Barbara M. and von Rheinbaben, Sabrina Freiin von and Lerch, Markus M. and Aghdassi, Ali Alexander and Weiss, Frank Ulrich and Sendler, Matthias (2022) Mobilization of CD11b(+)/Ly6c(hi) monocytes causes multi organ dysfunction syndrome in acute pancreatitis. FRONTIERS IN IMMUNOLOGY, 13: 991295. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
ObjectiveAcute 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. DesignOrgan 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. ResultsSimilar 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. ConclusionIn 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEASE ACTIVATION; B ACTIVATION; CELLS; CYTOMETRY; SEVERITY; INJURY; CCR2; MACROPHAGES; GUIDELINES; STIFFNESS; monocytes; MODS; acute pancreatitis; CCR2; MCP-1 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Feb 2024 13:44 |
| Last Modified: | 28 Feb 2024 13:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58249 |
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