Activated pulmonary intravascular macrophages increase pulmonary microvascular permeability in sheep

Abstract

Pulmonary intravascular macrophages (PIMs) reside in the alveolar capillaries of sheep lung. However, the role of PIMs activation in the mechanism of increasing pulmonary microvascular permeability is not clear. We determined, using awake sheep with chronic lung lymph fistulas, the effects of intraarterial infusion of latex beads emulsion (1 microns in diameter) on lung lymph-dynamics. Sheep were divided into 3 groups; control, low dose latex and high dose latex groups. In control group, their lymph-dynamics were stable during the experimental period. In low dose latex group (5.46 x 10(9) beads/kg), lung lymph flow increased during the infusion period, but lung lymph protein clearance did not change. In high dose latex group (5.46 x 10(10) beads/kg), lung lymph flow began to increase during the infusion period and remained high, and lung lymph protein clearance increased significantly during and after the infusion of latex beads emulsion. The latex beads mainly distributed to lungs, and 70% of the beads were caught by PIMs in their phagosomes. These findings suggest that the activation of PIMs through their phagocytic uptake of circulating microparticles increases pulmonary microvascular permeability.