Leukotrienes but not complement mediate limb ischemia-induced lung injury

Area of Science:

• Physiology
• Immunology
• Pathology

Background:

• Limb ischemia reperfusion triggers lung dysfunction.
• Polymorphonuclear leukocytes (PMN) and thromboxane (Tx) are implicated in this process.
• The role of chemoattractants like leukotriene B4 (LTB4) and complement (C) fragments is unclear.

Purpose of the Study:

• To investigate the intermediary role of LTB4 and C fragments in lung leukosequestration and respiratory dysfunction following limb ischemia reperfusion.

Main Methods:

• Anesthetized sheep underwent limb ischemia and reperfusion.
• Measurements included pulmonary artery pressure, plasma and lung lymph levels of LTB4 and TxB2, white blood cell (WBC) counts, and lung histology.
• Interventions included a lypoxygenase inhibitor (diethylcarbamazine) and decomplementation (cobra venom factor).
• Experiments were also conducted in C5-sufficient and C5-deficient mice.

Main Results:

• Reperfusion caused pulmonary hypertension, increased LTB4 and TxB2, elevated lung lymph flow, and leukosequestration in untreated sheep.
• Diethylcarbamazine treatment blunted these responses and reduced leukosequestration.
• Decomplementation did not prevent pulmonary hypertension or leukosequestration.
• Hind limb ischemia in mice led to significant lung leukosequestration, irrespective of C5 complement status.

Conclusions:

• Lung leukosequestration and increased microvascular permeability after limb ischemia are mediated by LTB4.
• The complement system does not play a significant role in this process.
• LTB4 is a key chemoattractant driving lung injury post-reperfusion.