Hyo In Kim1, Jinbong Park, Barbora Konecna, Wei Huang, Ingred Riça, David Gallo, Leo E Otterbein, Kiyoshi Itagaki, Carl J Hauser. 1. From the Department of Surgery (H.I.K., J.P., D.G., L.E.O., K.I., C.J.H.), Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts; Department of Pharmacology (J.P.), College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea; Institute of Molecular Biomedicine (B.K.), Faculty of Medicine, Comenius University, Bratislava, Slovakia; Department of Pharmacology (W.H.), Harbin Medical University-Daqing, Daqing, China; and The David H. Koch Institute for Integrative Cancer Research (I.R.), Massachusetts Institute of Technology, Cambridge, Massachusetts.
Abstract
BACKGROUND: Trauma increases susceptibility to secondary bacterial infections. The events suppressing antimicrobial immunity are unclear. Polymorphonuclear neutrophils (PMNs) migrate toward bacteria using chemotaxis, trap them in extracellular neutrophil extracellular traps, and kill them using respiratory burst (RB). We hypothesized that plasma and wound fluids from trauma patients alter PMN function. METHODS: Volunteer PMNs were incubated in plasma or wound fluids from trauma patients (days 0 and 1, days 2 and 3), and their functions were compared with PMNs incubated in volunteer plasma. Chemotaxis was assessed in transwells. Luminometry assessed total and intracellular RB responses to receptor-dependent and independent stimulants. Neutrophil extracellular trap formation was assessed using elastase assays. The role of tissue necrosis in creating functionally suppressive systemic PMN environments was assessed using a novel pig model where PMNs were incubated in uninjured pig plasma or plasma from pigs undergoing intraperitoneal instillation of liver slurry. RESULTS: Both plasma and wound fluids from trauma patients markedly suppress total PMN RB. Intracellular RB is unchanged, implicating suppression of extracellular RB. Wound fluids are more suppressive than plasma. Biofluids suppressed RB maximally early after injury and their effects decayed with time. Chemotaxis and neutrophil extracellular trap formation were suppressed by biofluids similarly. Lastly, plasma from pigs undergoing abdominal liver slurry instillation suppressed PMN RB, paralleling suppression by human trauma biofluids. CONCLUSION: Trauma plasma and wound fluids suppress RB and other key PMNs antimicrobial functions. Circulating suppressive signals can be derived from injured or necrotic tissue at wound sites, suggesting a key mechanism by which tissue injuries can put the host at risk for infection.
BACKGROUND: Trauma increases susceptibility to secondary bacterial infections. The events suppressing antimicrobial immunity are unclear. Polymorphonuclear neutrophils (PMNs) migrate toward bacteria using chemotaxis, trap them in extracellular neutrophil extracellular traps, and kill them using respiratory burst (RB). We hypothesized that plasma and wound fluids from trauma patients alter PMN function. METHODS: Volunteer PMNs were incubated in plasma or wound fluids from trauma patients (days 0 and 1, days 2 and 3), and their functions were compared with PMNs incubated in volunteer plasma. Chemotaxis was assessed in transwells. Luminometry assessed total and intracellular RB responses to receptor-dependent and independent stimulants. Neutrophil extracellular trap formation was assessed using elastase assays. The role of tissue necrosis in creating functionally suppressive systemic PMN environments was assessed using a novel pig model where PMNs were incubated in uninjured pig plasma or plasma from pigs undergoing intraperitoneal instillation of liver slurry. RESULTS: Both plasma and wound fluids from trauma patients markedly suppress total PMN RB. Intracellular RB is unchanged, implicating suppression of extracellular RB. Wound fluids are more suppressive than plasma. Biofluids suppressed RB maximally early after injury and their effects decayed with time. Chemotaxis and neutrophil extracellular trap formation were suppressed by biofluids similarly. Lastly, plasma from pigs undergoing abdominal liver slurry instillation suppressed PMN RB, paralleling suppression by human trauma biofluids. CONCLUSION: Trauma plasma and wound fluids suppress RB and other key PMNs antimicrobial functions. Circulating suppressive signals can be derived from injured or necrotic tissue at wound sites, suggesting a key mechanism by which tissue injuries can put the host at risk for infection.
Authors: C D Barrett; A T Hsu; C D Ellson; B Y Miyazawa; Y-W Kong; J D Greenwood; S Dhara; M D Neal; J L Sperry; M S Park; M J Cohen; B S Zuckerbraun; M B Yaffe Journal: Clin Exp Immunol Date: 2018-09-09 Impact factor: 4.330
Authors: Haipeng Li; Kiyoshi Itagaki; Nicola Sandler; David Gallo; Amanda Galenkamp; Elzbieta Kaczmarek; David H Livingston; Yi Zeng; Yen Ting Lee; I Tien Tang; Burak Isal; Leo Otterbein; Carl J Hauser Journal: J Trauma Acute Care Surg Date: 2015-02 Impact factor: 3.313