Normal mesenteric lymph blunts the pulmonary inflammatory response to endotoxin

Area of Science:

• Endocrinology
• Immunology
• Pathophysiology

Background:

• Hemorrhagic shock (HS) can lead to acute lung injury (ALI).
• Mesenteric lymph is a potential mediator linking gut ischemia and ALI post-HS.
• Focus has been on toxic mediators in post-shock mesenteric lymph (PSML), but loss of protective mediators in normal mesenteric lymph (NML) is also possible.

Purpose of the Study:

• To investigate the protective role of NML against inflammatory insults to pulmonary endothelium.
• To determine if this protective effect is diminished in PSML.
• To identify the components within NML responsible for this protective effect.

Main Methods:

• Primary human pulmonary endothelial cells (HMVECs) were incubated with NML or PSML from rats subjected to HS and resuscitation.
• Cells were stimulated with lipopolysaccharide (LPS) to induce inflammation.
• ICAM-1 surface expression was measured by flow cytometry.
• Lipoproteins were extracted from NML to assess their role in the protective effect.

Main Results:

• NML significantly decreased LPS-induced ICAM-1 expression on HMVECs by 71% compared to controls.
• PSML did not show this protective effect, with significantly higher ICAM-1 expression than NML.
• Extraction of lipoproteins from NML abolished its protective effect against LPS-induced ICAM-1 expression.

Conclusions:

• Lipoproteins in NML possess anti-inflammatory properties that reduce LPS-induced ICAM-1 expression in pulmonary endothelium.
• A reduction in these protective lipoproteins in mesenteric lymph following HS and resuscitation may contribute to PSML-induced lung injury.