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Posthemorrhagic shock mesenteric lymph primes circulating neutrophils and provokes lung injury
G Zallen1, E E Moore, J L Johnson
1Department of Surgery, Denver Health Medical Center and University of Colorado Health Sciences Center, Denver, Colorado 80204, USA.
Abstract:
Mesenteric lymph has recently been invoked as an avenue for gut-derived factors that may result in distant organ injury following hemorrhagic shock. We demonstrate that posthemorrhagic shock mesenteric lymph primes neutrophils (PMNs) and causes lung injury. Methods. Mesenteric lymph was collected from Sprague-Dawley rats from their mesenteric lymph duct prior to, during, and following hemorrhagic shock (MAP 40 for 90 min). The rats were then resuscitated with shed blood plus lactated Ringers (2X shed blood) over 3 h. Lung leak was assessed by transudation of Evan's blue dye into the alveolus as measured by bronchoalveolar lavage. Isolated human PMNs were incubated with 1 and 10% lymph; priming was measured by the fMLP (1 microM)-stimulated production of superoxide and surface expression of CD11b determined by flow cytometry. Results. Mesenteric lymph flow increased significantly during resuscitation: preshock 144.4 microl/h, shock 44.5 microl/h, resuscitation 566.6 microl/h. Furthermore, diversion of this lymph abrogated lung injury as compared to rats without lymph diversion. Finally, mesenteric lymph from postshock animals primed PMNs for superoxide production (nearly three times control cells) as well as increased surface expression of CD11b (2-fold over control). Conclusion. Mesenteric lymph primes PMNs and causes lung injury following hemorrhagic shock. Mesenteric lymph provides a conduit for proinflammatory mediators that may participate in the pathogenesis of MOF.
Insights
Mesenteric lymph from hemorrhagic shock primes neutrophils, leading to lung injury. This lymph acts as a pathway for inflammatory mediators contributing to distant organ damage.
Area of Science:
- Physiology
- Immunology
- Pathology
Background:
- Hemorrhagic shock can lead to distant organ injury.
- Mesenteric lymph is increasingly recognized as a potential pathway for gut-derived factors contributing to this injury.
Purpose of the Study:
- To investigate the role of mesenteric lymph in causing lung injury after hemorrhagic shock.
- To determine if mesenteric lymph primes neutrophils (PMNs) and contributes to inflammation.
Main Methods:
- Mesenteric lymph was collected from rats undergoing hemorrhagic shock and resuscitation.
- Isolated human PMNs were incubated with post-shock mesenteric lymph.
- Neutrophil priming was assessed by measuring superoxide production and CD11b surface expression.
Main Results:
- Mesenteric lymph flow significantly increased during resuscitation post-hemorrhagic shock.
- Diversion of mesenteric lymph reduced lung injury.
- Post-shock mesenteric lymph primed PMNs, increasing superoxide production and CD11b expression.
Conclusions:
- Mesenteric lymph plays a critical role in mediating lung injury following hemorrhagic shock.
- Mesenteric lymph serves as a conduit for pro-inflammatory mediators that can cause distant organ damage, potentially contributing to multiple organ failure (MOF).