Neutrophil CD18 expression and blockade after traumatic shock and endotoxin challenge

Timothy Fabian, Martin Croce, Ronald M. Stewart, Michael E. Dockter, Kenneth G. Proctor

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Objective: The expression of the leukocyte CD18 adhesion complex on polymorphonuclear leukocytes (PMNs) was measured, and the physiologic effects of blockade of the complex were studied after trauma and sepsis. Summary Background Data: Margination of PMNs occurs early during inflammation and depends, in part, on expression of the CD18 adhesion complex. Blockade of this adherence complex can reduce PMN-mediated damage. This study tests the hypothesis that PMN activation after resuscitated trauma produces an occult endothelial injury that increases the vulnerability to a delayed inflammatory stimulus. Methods: Anesthetized (fentanyl) mongrel pigs were sham injured or fluid resuscitated from soft tissue injury + 35% hemorrhage. Systemic blood was collected at 24-hour intervals from awake animals. The CD18 density on circulating PMNs was determined with flow cytometry using mean channel fluorescence (MCF). The CD18 receptors were blocked with monoclonal antibodies either immediately before trauma or immediately before an endotoxin (lipopolysaccharide [LPS]) challenge that was administered to all groups 3 days after the shock episode. Bronchoscopy was performed before trauma, pre-LPS, and post-LPS, and protein content was measured in bronchoalveolar lavage (BAL). Results: Mean channel fluorescence was reduced on PMNs for 48 hours in animals with trauma versus animals with sham injuries. Anti-CD18 therapy produced higher circulating PMN counts compared with nontreated sham or shock groups. The incremental rise of BAL protein after shock was prevented with anti-CD18; the increment after LPS was attenuated. Anti-CD18 was administered before trauma and reduced the fluids necessary to maintain cardiac filling pressures after LPS. Conclusions: These data suggest that PMNs are activated after resuscitation from traumatic shock and that these cells produce an endothelial injury that may increase the vulnerability to a septic challenge. The broad implications is that temporarily blocking PMN adhesiveness at the time of trauma might salvage some host tissue and reduce the incidence of septic complications in the post-trauma period.

Original languageEnglish (US)
Pages (from-to)552-563
Number of pages12
JournalAnnals of surgery
Volume220
Issue number4
DOIs
StatePublished - Jan 1 1994

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Traumatic Shock
Endotoxins
Neutrophils
Wounds and Injuries
Lipopolysaccharides
Shock
Bronchoalveolar Lavage
Fluorescence
Soft Tissue Injuries
Adhesiveness
Bronchoscopy
Fentanyl
Resuscitation
Sepsis
Flow Cytometry
Proteins
Leukocytes
Swine

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Neutrophil CD18 expression and blockade after traumatic shock and endotoxin challenge. / Fabian, Timothy; Croce, Martin; Stewart, Ronald M.; Dockter, Michael E.; Proctor, Kenneth G.

In: Annals of surgery, Vol. 220, No. 4, 01.01.1994, p. 552-563.

Research output: Contribution to journalArticle

Fabian, Timothy ; Croce, Martin ; Stewart, Ronald M. ; Dockter, Michael E. ; Proctor, Kenneth G. / Neutrophil CD18 expression and blockade after traumatic shock and endotoxin challenge. In: Annals of surgery. 1994 ; Vol. 220, No. 4. pp. 552-563.
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abstract = "Objective: The expression of the leukocyte CD18 adhesion complex on polymorphonuclear leukocytes (PMNs) was measured, and the physiologic effects of blockade of the complex were studied after trauma and sepsis. Summary Background Data: Margination of PMNs occurs early during inflammation and depends, in part, on expression of the CD18 adhesion complex. Blockade of this adherence complex can reduce PMN-mediated damage. This study tests the hypothesis that PMN activation after resuscitated trauma produces an occult endothelial injury that increases the vulnerability to a delayed inflammatory stimulus. Methods: Anesthetized (fentanyl) mongrel pigs were sham injured or fluid resuscitated from soft tissue injury + 35{\%} hemorrhage. Systemic blood was collected at 24-hour intervals from awake animals. The CD18 density on circulating PMNs was determined with flow cytometry using mean channel fluorescence (MCF). The CD18 receptors were blocked with monoclonal antibodies either immediately before trauma or immediately before an endotoxin (lipopolysaccharide [LPS]) challenge that was administered to all groups 3 days after the shock episode. Bronchoscopy was performed before trauma, pre-LPS, and post-LPS, and protein content was measured in bronchoalveolar lavage (BAL). Results: Mean channel fluorescence was reduced on PMNs for 48 hours in animals with trauma versus animals with sham injuries. Anti-CD18 therapy produced higher circulating PMN counts compared with nontreated sham or shock groups. The incremental rise of BAL protein after shock was prevented with anti-CD18; the increment after LPS was attenuated. Anti-CD18 was administered before trauma and reduced the fluids necessary to maintain cardiac filling pressures after LPS. Conclusions: These data suggest that PMNs are activated after resuscitation from traumatic shock and that these cells produce an endothelial injury that may increase the vulnerability to a septic challenge. The broad implications is that temporarily blocking PMN adhesiveness at the time of trauma might salvage some host tissue and reduce the incidence of septic complications in the post-trauma period.",
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N2 - Objective: The expression of the leukocyte CD18 adhesion complex on polymorphonuclear leukocytes (PMNs) was measured, and the physiologic effects of blockade of the complex were studied after trauma and sepsis. Summary Background Data: Margination of PMNs occurs early during inflammation and depends, in part, on expression of the CD18 adhesion complex. Blockade of this adherence complex can reduce PMN-mediated damage. This study tests the hypothesis that PMN activation after resuscitated trauma produces an occult endothelial injury that increases the vulnerability to a delayed inflammatory stimulus. Methods: Anesthetized (fentanyl) mongrel pigs were sham injured or fluid resuscitated from soft tissue injury + 35% hemorrhage. Systemic blood was collected at 24-hour intervals from awake animals. The CD18 density on circulating PMNs was determined with flow cytometry using mean channel fluorescence (MCF). The CD18 receptors were blocked with monoclonal antibodies either immediately before trauma or immediately before an endotoxin (lipopolysaccharide [LPS]) challenge that was administered to all groups 3 days after the shock episode. Bronchoscopy was performed before trauma, pre-LPS, and post-LPS, and protein content was measured in bronchoalveolar lavage (BAL). Results: Mean channel fluorescence was reduced on PMNs for 48 hours in animals with trauma versus animals with sham injuries. Anti-CD18 therapy produced higher circulating PMN counts compared with nontreated sham or shock groups. The incremental rise of BAL protein after shock was prevented with anti-CD18; the increment after LPS was attenuated. Anti-CD18 was administered before trauma and reduced the fluids necessary to maintain cardiac filling pressures after LPS. Conclusions: These data suggest that PMNs are activated after resuscitation from traumatic shock and that these cells produce an endothelial injury that may increase the vulnerability to a septic challenge. The broad implications is that temporarily blocking PMN adhesiveness at the time of trauma might salvage some host tissue and reduce the incidence of septic complications in the post-trauma period.

AB - Objective: The expression of the leukocyte CD18 adhesion complex on polymorphonuclear leukocytes (PMNs) was measured, and the physiologic effects of blockade of the complex were studied after trauma and sepsis. Summary Background Data: Margination of PMNs occurs early during inflammation and depends, in part, on expression of the CD18 adhesion complex. Blockade of this adherence complex can reduce PMN-mediated damage. This study tests the hypothesis that PMN activation after resuscitated trauma produces an occult endothelial injury that increases the vulnerability to a delayed inflammatory stimulus. Methods: Anesthetized (fentanyl) mongrel pigs were sham injured or fluid resuscitated from soft tissue injury + 35% hemorrhage. Systemic blood was collected at 24-hour intervals from awake animals. The CD18 density on circulating PMNs was determined with flow cytometry using mean channel fluorescence (MCF). The CD18 receptors were blocked with monoclonal antibodies either immediately before trauma or immediately before an endotoxin (lipopolysaccharide [LPS]) challenge that was administered to all groups 3 days after the shock episode. Bronchoscopy was performed before trauma, pre-LPS, and post-LPS, and protein content was measured in bronchoalveolar lavage (BAL). Results: Mean channel fluorescence was reduced on PMNs for 48 hours in animals with trauma versus animals with sham injuries. Anti-CD18 therapy produced higher circulating PMN counts compared with nontreated sham or shock groups. The incremental rise of BAL protein after shock was prevented with anti-CD18; the increment after LPS was attenuated. Anti-CD18 was administered before trauma and reduced the fluids necessary to maintain cardiac filling pressures after LPS. Conclusions: These data suggest that PMNs are activated after resuscitation from traumatic shock and that these cells produce an endothelial injury that may increase the vulnerability to a septic challenge. The broad implications is that temporarily blocking PMN adhesiveness at the time of trauma might salvage some host tissue and reduce the incidence of septic complications in the post-trauma period.

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