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Selective lung leukosequestration after complement activation
J M Klausner1, L Kobzik, C R Valeri
1Department of Surgery, Brigham and Women's Hosital, Boston, Massachusetts.
Abstract:
This study tests whether activated complement leads to a selective entrapment of polymorphonuclear leukocytes (PMN's) in the lungs. Awake sheep were infused for 5 min with zymosan-activated plasma (ZAP, 2.5 mg/ml) at a rate of 5 ml/min into the superior vena cava (IV, n = 4) or intra-arterially into the aortic arch or femoral artery (IA, n = 8). At the end of IV infusion, leukocyte counts fell from 8,862 to 1,631/mm3 (P less than 0.01). PMN counts across the lungs decreased by 74%. There were increases in plasma thromboxane (Tx) B2 from 114 to 2,733 pg/ml (P less than 0.01), mean pulmonary arterial pressure from 12 to 42 mmHg (P less than 0.01), and physiological shunt from 13 to 25% (P less than 0.05). Within 1 h lymph TxB2 levels had risen from 301 to 4,916 pg/ml (P less than 0.01), lung lymph flow (QL) rose from 3.7 to 11.1 ml/30 min (P less than 0.05), lymph-to-plasma protein ratio (L/P) remained unchanged at 0.63, and lymph protein clearance increased from 2.3 to 7.5 ml/30 min (P less than 0.05). Leukosequestration, quantitated by capillary PMN counting and by assaying the granulocyte marker myeloperoxidase, occurred relative to sham animals (P less than 0.05) in the lung and spleen but not in other organs. Intra-arterial ZAP infusion led to changes that were similar in magnitude and timing to the IV group.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Activated complement via zymosan-activated plasma (ZAP) infusion selectively traps polymorphonuclear leukocytes (PMNs) in sheep lungs. This process increases pulmonary arterial pressure and thromboxane B2 levels, indicating a significant inflammatory response.
Area of Science:
- Immunology
- Physiology
Background:
- The complement system plays a crucial role in innate immunity.
- Polymorphonuclear leukocytes (PMNs) are key immune cells involved in inflammation.
- Understanding complement activation's effects on leukocyte distribution is vital for inflammatory disease research.
Purpose of the Study:
- To investigate whether activated complement leads to selective entrapment of polymorphonuclear leukocytes (PMNs) in the lungs.
- To determine the physiological consequences of complement-mediated PMN sequestration in sheep.
Main Methods:
- Awake sheep were infused with zymosan-activated plasma (ZAP) intravenously or intra-arterially.
- Leukocyte and PMN counts were monitored before and after infusion.
- Plasma thromboxane B2 levels, pulmonary arterial pressure, and physiological shunt were measured.
- Lung lymph flow, lymph-to-plasma protein ratio, and lymph protein clearance were assessed.
- Leukosequestration was quantified using capillary PMN counting and myeloperoxidase assays.
Main Results:
- Intravenous ZAP infusion caused a significant drop in leukocyte counts and a 74% decrease in lung PMN counts.
- ZAP infusion led to increased plasma thromboxane B2, mean pulmonary arterial pressure, and physiological shunt.
- Lung lymph flow and lymph protein clearance increased, while the lymph-to-plasma protein ratio remained unchanged.
- Leukosequestration was confirmed in the lung and spleen, but not other organs.
Conclusions:
- Activated complement selectively sequesters polymorphonuclear leukocytes (PMNs) in the lungs.
- This sequestration is associated with increased pulmonary arterial pressure and thromboxane B2 production.
- The findings highlight a mechanism by which complement activation can trigger acute inflammatory responses in the pulmonary vasculature.