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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.

Journal of Applied Physiology (Bethesda, Md. : 1985)
|July 1, 1988
PubMed
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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.

Related Experiment Videos

  • 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.