Prevention of acute lung injury in swine: depletion of pulmonary intravascular macrophages using liposomal clodronate

Gaca, Jeffrey G.; Palestrant, Daniel; Lukes, Daniel; Olausson, Michael; Parker, William; Davis, Robert D.

doi:10.1016/s0022-4804(03)00142-2

Cited by 51 publications

(49 citation statements)

References 28 publications

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“…The immunosuppressive regimen and transplant operations were conduced as previously described by this laboratory (35). Porcine macrophages were depleted from porcine lungs using liposomal clodronate administered intravenously in four doses over 2 days preceding the transplant, as described previously (36,38). Graft failure was defined as a decrease in graft flow below 50 mL/min.…”

Section: Methodsmentioning

confidence: 99%

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

Cantu

Balsara

et al. 2007

American Journal of Transplantation

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Porcine von Willebrand factor (vWF) activates human and primate platelets. Having determined the importance of pulmonary intravascular macrophages (PIMs) in pulmonary xenotransplantation, we evaluated whether, in the absence of PIMs, vWF might play a role in pulmonary xenograft dysfunction.Utilizing a left single-lung transplant model, baboons depleted of anti-a Gal antibodies received lungs from either vWF-deficient (n = 2); MCP-expressing (n = 5); MCP PIM-depleted (n = 5); or vWF-deficient PIMdepleted swine (n = 3).Two out of three of the PIM-depleted, pvWF deficient grafts survived longer than any previously reported pulmonary xenografts, including PIM-depleted xenografts expressing human complement regulatory proteins. Depletion of PIM's from vWF-deficient lungs, like depletion of PIM's from hMCP lungs, resulted in abrogation of the coagulopathy associated with pulmonary xenotransplantation.Thus, in terms of pulmonary graft survival, control of adverse reactions involving pvWF appears to be equally or even more important than is complement regulation using hMCP expression. However, based on the rapid failure of PIM-sufficient, pvWFdeficient pulmonary xenografts, pVWF-deficient pulmonary xenografts appear to be particularly sensitive to macrophage-mediated damage. These data provide initial evidence that vWF plays a role in the 'delayed' (24 h) dysfunction observed in pulmonary xenotransplantation using PIM depleted hMCP organs.

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Section: Methodsmentioning

confidence: 99%

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

Cantu

Balsara

et al. 2007

American Journal of Transplantation

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“…(63) or hyperacute pulmorary xenograft rejection in pigs (49). PIM depletion in sheep led to the loss of pulmonary vaso-responsiveness, whose return coincided with PIM repopulation (67).…”

Section: Secretory Products and Mediatorsmentioning

confidence: 99%

Pulmonary intravascular macrophages: prime suspects as cellular mediators of porcine CARPA

Csukás

Urbanics²,

Weber

et al. 2015

European Journal of Nanomedicine

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Pigs provide a highly sensitive and quantitative in vivo model for complement (C) activation-related pseudoallergy (CARPA), a hypersensitivity reaction caused by some state-of-art nanomedicines. In an effort to understand the mechanism of the pigs' unique sensitivity for CARPA, this review focuses on pulmonary intravascular macrophages (PIMs), which are abundantly present in the lung of pigs. These cells represent a macrophage subpopulation whose unique qualities explain the characteristic symptoms of CARPA in this species, most importantly the rapidly (within minutes) developing pulmonary vasoconstriction, leading to elevation of pulmonary arterial pressure. The unique qualities of PIM cells include the following; 1) they are strongly adhered to the capillary walls via desmosomelike intercellular adhesion plaques, which secure stable and lasting direct exposition of the bulk of these cells to the blood stream; 2) their ruffled surface engaged in intense phagocytic activity ensures efficient binding and phagocytosis of nanoparticles; 3) PIM cells express anaphylatoxin receptors, this way C activation can trigger these cells, 4) they also express pattern recognition molecules on their surface, whose engagement with certain coated nanoparticles may also activate these cells or act in synergy with anaphylatoxins and, finally 5) their high metabolic activity and capability for immediate secretion of vasoactive mediators upon stimulation explain the circulatory blockage and other robust physiological effects that their stimulation may cause. These qualities taken together with reports on liposome uptake by PIM cells during CARPA and the possible presence of these cells in human lung suggests that PIM cells may be a potential therapeutic target against CARPA.

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“…These and other PIM-containing species, and rats upon recruitment of PIMs under physiological stress, are highly susceptible to acute lung inflammation (19). The role of macrophages including PIMs in inflammation has been studied through their in vivo depletion with chemicals such as gadolinium chloride (GC) and clodronate (18,48,54). We have used GC, a heavy metal lanthanide, to deplete PIMs in cattle, horses and sheep (33,47,48).…”

mentioning

confidence: 99%

Pulmonary intravascular macrophages as proinflammatory cells in heaves, an asthma-like equine disease

Aharonson-Raz

Lohmann

Townsend

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Prevention of acute lung injury in swine: depletion of pulmonary intravascular macrophages using liposomal clodronate

Cited by 51 publications

References 28 publications

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

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

Pulmonary intravascular macrophages: prime suspects as cellular mediators of porcine CARPA

Pulmonary intravascular macrophages as proinflammatory cells in heaves, an asthma-like equine disease

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