Effect of particles on sheep lung hemodynamics parallels depletion and recovery of intravascular macrophages

Abstract

We previously showed in newborn lambs that the pulmonary hemodynamic responses to foreign particulate matter (liposomes; Monastral blue) developed in parallel with the maturation of the pulmonary intravascular macrophage system. We now report our use of the liposome-encapsulated heavy-metal-chelating agent dichloromethylene diphosphonate to deplete the intravascular macrophages of small lambs. Functionally and by quantitative histology, we depleted the vast majority of the intravascular macrophages (71% by Monastral blue particle retention, n = 22; 77% by histology; n = 2). Depletion success increased to > 90% as we optimized the liposome-depletion regime. Recovery of the lung hemodynamic response began within 3 days. By 2 wk, the functional responses had fully recovered (n = 8), and, according to quantitative histology, the macrophage population (n = 2) had recovered 65%. Macrophage depletion in lambs is relatively inexpensive and easy to achieve. It is a safe procedure and is followed by full recovery in approximately 2 wk, provided that an aseptic technique is used to prevent bacteremia.

Melanin Granules of Retinal Pigment Epithelium are Connected with the Lysosomal Degradation Pathway

“…This general finding excludes the possibility of simultaneous uptake of melanin delivered from damaged cells and injected material. MB is a non-toxic dye (Desemone et al, 1990) that is used to detect endocytosis or leakage of blood vessels (Baluk et al, 1997 ;Desemone et al, 1990 ;Sone, Nicolaysen and Staub, 1997). The transport into the melanin granules is not mediated by a toxic effect of MB because gold particles were also present in melanin granules in the experiments without MB.…”

Prolonged Function of Macrophage, von Willebrand Factor-Deficient Porcine Pulmonary Xenografts

“…Using a technique to deplete macrophages using liposomal clodronate developed by Van Rooijen (31,32), Staub was able to demonstrate in PIM depleted versus nondepleted sheep, LPS infusion resulted in complete abrogation of increases in PVR and >90% attenuation of the capillary leak (33,34).…”

Depletion of pulmonary intravascular macrophages partially inhibits lipopolysaccharide-induced lung inflammation in horses

“…But pulmonary hypertension is observed in two-week old lambs that have sequestered PIMs. This hypertensive response, however, is abolished following removal of PIMs [27]. In vitro evidence shows that porcine PIMs can metabolise arachidonic acid [7,8].…”