William Royster1, Mahendar Ochani2, Monowar Aziz1, Ping Wang3. 1. Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, New York; Elmezzi Graduate School of Molecular Medicine, Manhasset, New York; Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, Manhasset, New York. 2. Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, New York. 3. Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, New York; Elmezzi Graduate School of Molecular Medicine, Manhasset, New York; Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, Manhasset, New York; Department of Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York. Electronic address: pwang@northwell.edu.
Abstract
BACKGROUND: Acute mesenteric ischemia is a common surgical emergency. Restoration of blood flow is a critical objective of treating this pathology. However, many patients suffer from ischemia-reperfusion (I/R) injuries at the time of revascularization, requiring prolonged hospitalizations. B-1a cells are a subtype of B lymphocytes with roles in regulating inflammation and tissue injury by spontaneous release of natural IgM and IL-10. We hypothesized that treatment with B-1a cells protects mice from intestinal I/R. METHODS: Mesenteric ischemia was induced in mice by placing a vascular clip on the superior mesenteric artery for 60 minutes. At the time of reperfusion, B-1a cells or PBS control were instilled into the peritoneal cavity (PerC) of mice. PerC lavage, blood, intestine, and lungs were collected 4 h after reperfusion. Serum organ injury and inflammatory markers such as ALT, AST, LDH, lactate, IL-6, as well as lung and gut histology and myeloperoxidase (MPO) were assessed. RESULTS: In intestinal I/R, B-1a cell frequency and number in the PerC were significantly decreased compared to sham-operated mice. There was an increase in the serum levels of ALT, AST, LDH, lactate, and IL-6 when comparing the vehicle group with the sham group. These increases were significantly reduced in the B-1a cell treated group. B-1a cell treatment significantly decreased the intestine and lung injury scores as well as MPO content, compared to vehicle treated mice. B-1a cell treatment resulted in a reduction of apoptotic cells in these tissues. Serum IgM levels were decreased in intestinal I/R, while treatment with B-1a cells significantly increased their levels towards normal levels. CONCLUSIONS: B-1a cell treatment at the time of mesenteric reperfusion ameliorates end organ damage and reduces systemic inflammation through the improvement of serum IgM levels. Preserving B-1a cells pool could serve as a novel therapeutic avenue in intestinal I/R injury.
BACKGROUND: Acute mesenteric ischemia is a common surgical emergency. Restoration of blood flow is a critical objective of treating this pathology. However, many patients suffer from ischemia-reperfusion (I/R) injuries at the time of revascularization, requiring prolonged hospitalizations. B-1a cells are a subtype of B lymphocytes with roles in regulating inflammation and tissue injury by spontaneous release of natural IgM and IL-10. We hypothesized that treatment with B-1a cells protects mice from intestinal I/R. METHODS: Mesenteric ischemia was induced in mice by placing a vascular clip on the superior mesenteric artery for 60 minutes. At the time of reperfusion, B-1a cells or PBS control were instilled into the peritoneal cavity (PerC) of mice. PerC lavage, blood, intestine, and lungs were collected 4 h after reperfusion. Serum organ injury and inflammatory markers such as ALT, AST, LDH, lactate, IL-6, as well as lung and gut histology and myeloperoxidase (MPO) were assessed. RESULTS: In intestinal I/R, B-1a cell frequency and number in the PerC were significantly decreased compared to sham-operated mice. There was an increase in the serum levels of ALT, AST, LDH, lactate, and IL-6 when comparing the vehicle group with the sham group. These increases were significantly reduced in the B-1a cell treated group. B-1a cell treatment significantly decreased the intestine and lung injury scores as well as MPO content, compared to vehicle treated mice. B-1a cell treatment resulted in a reduction of apoptotic cells in these tissues. Serum IgM levels were decreased in intestinal I/R, while treatment with B-1a cells significantly increased their levels towards normal levels. CONCLUSIONS: B-1a cell treatment at the time of mesenteric reperfusion ameliorates end organ damage and reduces systemic inflammation through the improvement of serum IgM levels. Preserving B-1a cells pool could serve as a novel therapeutic avenue in intestinal I/R injury.
Authors: Philipp J Rauch; Aleksey Chudnovskiy; Clinton S Robbins; Georg F Weber; Martin Etzrodt; Ingo Hilgendorf; Elizabeth Tiglao; Jose-Luiz Figueiredo; Yoshiko Iwamoto; Igor Theurl; Rostic Gorbatov; Michael T Waring; Adam T Chicoine; Majd Mouded; Mikael J Pittet; Matthias Nahrendorf; Ralph Weissleder; Filip K Swirski Journal: Science Date: 2012-01-12 Impact factor: 47.728
Authors: Aditi Upadhye; Prasad Srikakulapu; Ayelet Gonen; Sabrina Hendrikx; Heather M Perry; Anh Nguyen; Chantel McSkimming; Melissa A Marshall; James C Garmey; Angela M Taylor; Timothy P Bender; Sotirios Tsimikas; Nichol E Holodick; Thomas L Rothstein; Joseph L Witztum; Coleen A McNamara Journal: Circ Res Date: 2019-09-24 Impact factor: 17.367