Stimulation of pulmonary intravascular macrophages increases microvascular permeability in awake sheep

The purpose of this study is to determine if stimulation of pulmonary intravascular macrophages (PIMs) increase microvascular permeability in sheep. We infused latex microbeads, 1 micron in diameter, for 1 hr continuously and analysed lung hemodynamic and lymph-dynamic changes. More than 70% of latex microbeads in the lung were assigned to PIMs, and caught in their phagosomes as determined by morphological examination. This implies that infused latex microbeads predominantly stimulate PIMs. Pulmonary arterial pressure increased during the infusion period, and returned to baseline after the infusion period. Lung lymph flow increased and remained high while the lymph to plasma protein ratio ultimately increased above baseline. This implies that infusion of latex microbeads increases pulmonary microvascular permeability. The increase in lung lymph protein clearance was blocked completely by pretreatment with indomethacin, but not with a thromboxane synthetase inhibitor (OKY-046). These data indicate that the increase in microvascular permeability is mediated by an arachidonic acid cyclooxygenase metabolites but not by thromboxane. We conclude that PIMs can act as an initiator to increase pulmonary microvascular permeability by releasing arachidonic acid cyclooxygenase metabolites through their stimulation with latex beads.