Selective lung leukosequestration after complement activation

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 < 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 < 0.01), mean pulmonary arterial pressure from 12 to 42 mmHg (P < 0.01), and physiological shunt from 13 to 25% (P < 0.05). Within 1 h lymph TxB2 levels had risen from 301 to 4,916 pg/ml (P < 0.01), lung lymph flow (.ovrhdot.QL) rose from 3.7 to 11.1 ml/30 min (P < 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 < 0.05). Leukosequestration, quantitated by capillary PMN counting and by assaying the granulocyte marker myeloperoxidase, occurred relative to sham animals (P < 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. In a non-ZAP-infused control group (n = 3) recruitment of the lung vasculature by left atrial balloon inflation led to a rise in .ovrhdot.QL from 2.4 to 8.2 ml/30 min, whereas L/P declined from 0.62 to 0.25, suggesting that the protein-rich lymph flow after IV or IA ZAP reflects increased microvascular permeability. TxB2 inhibition attentuated the pulmonary hypertension and increased shunting and the altered permeability in IV and IA groups. These data indicate that the pulmonary microvascular bed selectively entraps complement-activated PMN''s.