Effect of complement activation with cobra venom factor on pulmonary vascular permeability.

We examined the effect of acute complement activation on lung vascular permeability to proteins in awake sheep prepared with lung lymph fistulas. Complement was activated by cobra venom factor (CVF) infusion (400 U/kg for 1 h iv). Studies were made in two groups of sheep: 1) infusion of CVF containing the endogenous phospholipase A2 (PLA2) (n = 6); and 2) infusion of CVF pretreated with bromophenacyl bromide to inhibit PLA2 activity (n = 5). Intravascular complement activation transiently increased mean pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (PVR) in both groups. Pulmonary lymph flow (Qlym) and lymph protein clearance (Qlym X lymph-to-plasma protein concentration ratio) were also transiently increased in both groups. Pulmonary vascular permeability to proteins was assessed by raising left atrial pressure and determining the lymph-to-plasma protein concentration ratio (L/P) at maximal Qlym. In both groups the L/P at maximal Qlym was not different from normal. In a separate group (n = 4), CVF-induced complement activation was associated with 111In-oxine granulocyte sequestration in the lungs. In vitro plasma from CVF-treated animals aggregated neutrophils but did not stimulate neutrophils to produce superoxide anion generation. Therefore, CVF-induced complement activation results in pulmonary neutrophil sequestration and in increases in PVR and lymph protein clearance. The increase in lymph protein clearance is due to increased pulmonary microvascular pressure and not increased vascular permeability to proteins.