Related Experiment Videos
Neutrophil CD18 expression and blockade after traumatic shock and endotoxin challenge
T C Fabian1, M A Croce, R M Stewart
1Department of Surgery, University of Tennessee Health Science Center, Memphis.
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 implication 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.
Insights
Blocking leukocyte CD18 adhesion complex after trauma reduces inflammation and injury. This intervention may prevent post-trauma complications and improve outcomes in critically ill patients.
Area of Science:
- Immunology
- Trauma research
- Critical care medicine
Background:
- Polymorphonuclear leukocytes (PMNs) margination is crucial in inflammation, partly due to the CD18 adhesion complex.
- Blocking CD18 can mitigate PMN-mediated tissue damage.
- This study investigates if trauma-induced PMN activation leads to endothelial injury, increasing susceptibility to secondary inflammatory challenges.
Purpose of the Study:
- To measure CD18 expression on PMNs post-trauma and sepsis.
- To evaluate the physiological effects of blocking the CD18 complex.
- To test if PMN activation after trauma increases vulnerability to subsequent inflammatory stimuli.
Main Methods:
- Mongrel pigs underwent sham injury or trauma with hemorrhage and fluid resuscitation.
- CD18 expression on circulating PMNs was quantified using flow cytometry.
- Monoclonal antibodies blocked CD18 receptors before trauma or lipopolysaccharide (LPS) challenge.
- Bronchoalveolar lavage (BAL) protein content was measured to assess lung injury.
Main Results:
- Trauma reduced CD18 expression on PMNs for 48 hours.
- Anti-CD18 therapy increased circulating PMN counts compared to controls.
- Anti-CD18 prevented increased BAL protein post-shock and attenuated it post-LPS.
- Pre-trauma anti-CD18 administration reduced fluid requirements after LPS challenge.
Conclusions:
- PMN activation post-resuscitation from traumatic shock contributes to endothelial injury.
- This injury heightens susceptibility to sepsis.
- Temporary blockade of PMN adhesiveness during trauma may preserve host tissue and decrease septic complications.