P-Selectin Is Critical for de Novo Pulmonary Arterial Thrombosis Following Blunt Thoracic Trauma

Linda M. Schutzman, Robert R. Rigor, Nasim Khosravi, Joseph M Galante, Ian Elliott Brown

Research output: Contribution to journalArticle

Abstract

BACKGROUND Thromboembolic events within the pulmonary arterial vasculature are a troublesome complication of severe blunt thoracic trauma. Mechanisms underlying these events are currently in question as pulmonary thromboembolic events in this particular trauma population tend to be diagnosed more rapidly, more frequently and without an associated systemic thrombosis. This study investigates the role of P-selectin in thrombus formation through the use of in vivo blocking antibodies. We hypothesize that P-selectin plays a pivotal role in de novo pulmonary arterial thrombosis following blunt thoracic trauma. METHODS A murine weight-drop model of lateral blunt thoracic trauma was used. Wild-type mice in the experimental group were given blocking antibodies against P-selectin prior to the trauma. All mice were euthanized at 24 hours for evaluation with hematoxylin-eosin staining or immunofluorescent staining for fibrin and P-selectin. RESULTS Injured mice that did not receive the P-selectin antibody showed a robust fourfold to fivefold increase in fibrin accumulation in both coup and contrecoup tissues (fluorescence per um of arterial wall) compared to uninjured sham mice. In contrast, mice pretreated with P-selectin blocking antibody showed no significant increase in fibrin accumulation on either side of the lungs after blunt thoracic trauma. No difference in mean fibrin deposition was found between sham controls that received the P-selectin-blocking antibody and those that received an isotype control antibody. CONCLUSION P-selectin expression increases at the pulmonary arterial luminal surface following blunt thoracic trauma. In addition, P-selectin-blocking in vivo prevents pulmonary arterial fibrin accumulation after blunt thoracic trauma, confirming that P-selectin is necessary for de novo pulmonary arterial thrombosis after traumatic injury.

Original languageEnglish (US)
Pages (from-to)583-590
Number of pages8
JournalJournal of Trauma and Acute Care Surgery
Volume86
Issue number4
DOIs
StatePublished - Apr 1 2019

Fingerprint

P-Selectin
Thrombosis
Thorax
Lung
Wounds and Injuries
Fibrin
Blocking Antibodies
Staining and Labeling
Antibodies
Hematoxylin
Eosine Yellowish-(YS)
Fluorescence
Weights and Measures

Keywords

  • blunt thoracic trauma
  • clot
  • P-selectin
  • pulmonary embolism
  • thrombosis

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

Cite this

P-Selectin Is Critical for de Novo Pulmonary Arterial Thrombosis Following Blunt Thoracic Trauma. / Schutzman, Linda M.; Rigor, Robert R.; Khosravi, Nasim; Galante, Joseph M; Brown, Ian Elliott.

In: Journal of Trauma and Acute Care Surgery, Vol. 86, No. 4, 01.04.2019, p. 583-590.

Research output: Contribution to journalArticle

@article{881bcae058a34cefadc8ded5ed17e5b7,
title = "P-Selectin Is Critical for de Novo Pulmonary Arterial Thrombosis Following Blunt Thoracic Trauma",
abstract = "BACKGROUND Thromboembolic events within the pulmonary arterial vasculature are a troublesome complication of severe blunt thoracic trauma. Mechanisms underlying these events are currently in question as pulmonary thromboembolic events in this particular trauma population tend to be diagnosed more rapidly, more frequently and without an associated systemic thrombosis. This study investigates the role of P-selectin in thrombus formation through the use of in vivo blocking antibodies. We hypothesize that P-selectin plays a pivotal role in de novo pulmonary arterial thrombosis following blunt thoracic trauma. METHODS A murine weight-drop model of lateral blunt thoracic trauma was used. Wild-type mice in the experimental group were given blocking antibodies against P-selectin prior to the trauma. All mice were euthanized at 24 hours for evaluation with hematoxylin-eosin staining or immunofluorescent staining for fibrin and P-selectin. RESULTS Injured mice that did not receive the P-selectin antibody showed a robust fourfold to fivefold increase in fibrin accumulation in both coup and contrecoup tissues (fluorescence per um of arterial wall) compared to uninjured sham mice. In contrast, mice pretreated with P-selectin blocking antibody showed no significant increase in fibrin accumulation on either side of the lungs after blunt thoracic trauma. No difference in mean fibrin deposition was found between sham controls that received the P-selectin-blocking antibody and those that received an isotype control antibody. CONCLUSION P-selectin expression increases at the pulmonary arterial luminal surface following blunt thoracic trauma. In addition, P-selectin-blocking in vivo prevents pulmonary arterial fibrin accumulation after blunt thoracic trauma, confirming that P-selectin is necessary for de novo pulmonary arterial thrombosis after traumatic injury.",
keywords = "blunt thoracic trauma, clot, P-selectin, pulmonary embolism, thrombosis",
author = "Schutzman, {Linda M.} and Rigor, {Robert R.} and Nasim Khosravi and Galante, {Joseph M} and Brown, {Ian Elliott}",
year = "2019",
month = "4",
day = "1",
doi = "10.1097/TA.0000000000002166",
language = "English (US)",
volume = "86",
pages = "583--590",
journal = "Journal of Trauma and Acute Care Surgery",
issn = "2163-0755",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - P-Selectin Is Critical for de Novo Pulmonary Arterial Thrombosis Following Blunt Thoracic Trauma

AU - Schutzman, Linda M.

AU - Rigor, Robert R.

AU - Khosravi, Nasim

AU - Galante, Joseph M

AU - Brown, Ian Elliott

PY - 2019/4/1

Y1 - 2019/4/1

N2 - BACKGROUND Thromboembolic events within the pulmonary arterial vasculature are a troublesome complication of severe blunt thoracic trauma. Mechanisms underlying these events are currently in question as pulmonary thromboembolic events in this particular trauma population tend to be diagnosed more rapidly, more frequently and without an associated systemic thrombosis. This study investigates the role of P-selectin in thrombus formation through the use of in vivo blocking antibodies. We hypothesize that P-selectin plays a pivotal role in de novo pulmonary arterial thrombosis following blunt thoracic trauma. METHODS A murine weight-drop model of lateral blunt thoracic trauma was used. Wild-type mice in the experimental group were given blocking antibodies against P-selectin prior to the trauma. All mice were euthanized at 24 hours for evaluation with hematoxylin-eosin staining or immunofluorescent staining for fibrin and P-selectin. RESULTS Injured mice that did not receive the P-selectin antibody showed a robust fourfold to fivefold increase in fibrin accumulation in both coup and contrecoup tissues (fluorescence per um of arterial wall) compared to uninjured sham mice. In contrast, mice pretreated with P-selectin blocking antibody showed no significant increase in fibrin accumulation on either side of the lungs after blunt thoracic trauma. No difference in mean fibrin deposition was found between sham controls that received the P-selectin-blocking antibody and those that received an isotype control antibody. CONCLUSION P-selectin expression increases at the pulmonary arterial luminal surface following blunt thoracic trauma. In addition, P-selectin-blocking in vivo prevents pulmonary arterial fibrin accumulation after blunt thoracic trauma, confirming that P-selectin is necessary for de novo pulmonary arterial thrombosis after traumatic injury.

AB - BACKGROUND Thromboembolic events within the pulmonary arterial vasculature are a troublesome complication of severe blunt thoracic trauma. Mechanisms underlying these events are currently in question as pulmonary thromboembolic events in this particular trauma population tend to be diagnosed more rapidly, more frequently and without an associated systemic thrombosis. This study investigates the role of P-selectin in thrombus formation through the use of in vivo blocking antibodies. We hypothesize that P-selectin plays a pivotal role in de novo pulmonary arterial thrombosis following blunt thoracic trauma. METHODS A murine weight-drop model of lateral blunt thoracic trauma was used. Wild-type mice in the experimental group were given blocking antibodies against P-selectin prior to the trauma. All mice were euthanized at 24 hours for evaluation with hematoxylin-eosin staining or immunofluorescent staining for fibrin and P-selectin. RESULTS Injured mice that did not receive the P-selectin antibody showed a robust fourfold to fivefold increase in fibrin accumulation in both coup and contrecoup tissues (fluorescence per um of arterial wall) compared to uninjured sham mice. In contrast, mice pretreated with P-selectin blocking antibody showed no significant increase in fibrin accumulation on either side of the lungs after blunt thoracic trauma. No difference in mean fibrin deposition was found between sham controls that received the P-selectin-blocking antibody and those that received an isotype control antibody. CONCLUSION P-selectin expression increases at the pulmonary arterial luminal surface following blunt thoracic trauma. In addition, P-selectin-blocking in vivo prevents pulmonary arterial fibrin accumulation after blunt thoracic trauma, confirming that P-selectin is necessary for de novo pulmonary arterial thrombosis after traumatic injury.

KW - blunt thoracic trauma

KW - clot

KW - P-selectin

KW - pulmonary embolism

KW - thrombosis

UR - http://www.scopus.com/inward/record.url?scp=85063712369&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063712369&partnerID=8YFLogxK

U2 - 10.1097/TA.0000000000002166

DO - 10.1097/TA.0000000000002166

M3 - Article

C2 - 30562326

AN - SCOPUS:85063712369

VL - 86

SP - 583

EP - 590

JO - Journal of Trauma and Acute Care Surgery

JF - Journal of Trauma and Acute Care Surgery

SN - 2163-0755

IS - 4

ER -