Obstruction of Capillaries by circulating large Monocytes causes Multi Organ Dysfunction Syndrome (MODS) in Acute Pancreatitis

Abstract

Acute pancreatitis (AP) is an inflammatory disorder, the severe form of which is burdened with high mortality. The pathogenesis of severity-driving organ manifestations, such as respiratory and renal failure, is unknown. We used samples from 300 pancreatitis patients and an experimental model of severe acute pancreatitis (SAP) to characterize severity-dependent cytokine profiles and resident/circulating immune cell populations by flow-cytometry and real-time- fluorescence and deformability-cytometry analysis. On functional, immunolabelling and in-vivo antibody-depletion experiments we confirmed the role of inflammatory cells in pancreatitis but found neither T-cells, Ly6g+-neutrophils or granulocytic-myeloid-derived-suppressor-cells (gMDSC) but a massive mobilisation of CCR2+/CD11b+-monocytes to be responsible for lung and kidney injury during SAP. Real-time-fluorescence and deformability-cytometry analyses suggest, that the physical properties of monocytes, especially their large size, results in an obstruction of the fine capillary-systems of the lung or of the kidney glomeruli. Their selective depletion can represent a promising treatment strategy for pancreatitis as well as other inflammation-related disorders.