title: Modulation of syndecan-1 shedding after hemorrhagic shock and resuscitation.
abstract: The early use of fresh frozen plasma as a resuscitative agent after hemorrhagic shock has been associated with improved survival, but the mechanism of protection is unknown. Hemorrhagic shock causes endothelial cell dysfunction and we hypothesized that fresh frozen plasma would restore endothelial integrity and reduce syndecan-1 shedding after hemorrhagic shock. A prospective, observational study in severely injured patients in hemorrhagic shock demonstrated significantly elevated levels of syndecan-1 (554±93 ng/ml) after injury, which decreased with resuscitation (187±36 ng/ml) but was elevated compared to normal donors (27±1 ng/ml). Three pro-inflammatory cytokines, interferon-γ, fractalkine, and interleukin-1β, negatively correlated while one anti-inflammatory cytokine, IL-10, positively correlated with shed syndecan-1. These cytokines all play an important role in maintaining endothelial integrity. An in vitro model of endothelial injury then specifically examined endothelial permeability after treatment with fresh frozen plasma orlactated Ringers. Shock or endothelial injury disrupted junctional integrity and increased permeability, which was improved with fresh frozen plasma, but not lactated Ringers. Changes in endothelial cell permeability correlated with syndecan-1 shedding. These data suggest that plasma based resuscitation preserved endothelial syndecan-1 and maintained endothelial integrity, and may help to explain the protective effects of fresh frozen plasma after hemorrhagic shock.
authors: Department of Surgery, The University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors: Ricky J
authors: RJ
authors: Haywood-Watson
authors: John B
authors: JB
authors: Holcomb
authors: Ernest A
authors: EA
authors: Gonzalez
authors: Zhanglong
authors: Z
authors: Peng
authors: Shibani
authors: S
authors: Pati
authors: Pyong Woo
authors: PW
authors: Park
authors: WeiWei
authors: W
authors: Wang
authors: Ana Maria
authors: AM
authors: Zaske
authors: Tyler
authors: T
authors: Menge
authors: Rosemary A
authors: RA
authors: Kozar
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D004727:Endothelium / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008954:Models, Biological; D010949:Plasma; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D053668:Syndecan-1 / Q000378:metabolism*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D016207:Cytokines; D053668:Syndecan-1; D000099152:Cadherin 5