Mast cell-Ito cell pairings found in the Disse's spaces in the liver of the beagle dog.

Kobayashi, Kan; Sakata, Koichi; Miyata, Ken; Iino, Takeshi; Iwasaki, Shigeo; Takahashi, Keiichi

doi:10.1679/aohc.48.483

Cited by 9 publications

(6 citation statements)

References 17 publications

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“…In addition, mast cells are particularly dense around the central veins compared to perilobular sinusoids in dogs 25,28 . Mast cells are not generally observed in these areas and are occasionally found only in the Glisson's sheath in other animal species including humans 26,29 . Liposomal formulations are known to activate mast cells following C3a induction during the process of CARPA [18][19][20][21] , and the severity depends on the physicochemical properties of liposomes 11,12 .…”

Section: Discussionmentioning

confidence: 98%

Dog-specific hemorrhagic changes induced by liposomal formulations, in the liver and the gallbladder

et al. 2020

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Although several liposomal drugs, including liposomal doxorubicin, have been approved, the etiology of the pathological responses caused by their physicochemical properties remains unknown. Herein, we investigated the pathological changes in the liver and the gallbladder of dogs following a single injection of liposomal doxorubicin (1 or 2.5 mg/kg) or an empty liposomal formulation (i.e., liposomal formulation without doxorubicin, ca. 21 mg/kg as lipid content). Injection of liposomal doxorubicin or the empty liposomal formulation induced hemorrhagic changes in the liver and the gallbladder. These changes were accompanied by minimal cellular infiltration with no obvious changes in the blood vessels. As there were no differences in the incidence and severity of hemorrhage between the groups administered comparable amounts of total lipid, the physicochemical properties of the liposomal formulation rather than an active pharmacological ingredient, doxorubicin, were associated with the hemorrhagic changes. Furthermore, decreased cytoplasmic granules with low electron density in mast cells beneath the endothelium of the hepatic vein were observed in the liver of dogs treated with liposomal doxorubicin or empty liposomal formulation. Injection of compound 48/80, a histamine releaser induced comparable hemorrhage in dogs, implying that hemorrhage caused by injection of liposomal doxorubicin or the empty liposomal formulation could be attributed to the histamine released from mast cells. The absence of similar hemorrhagic lesions in other species commonly used in toxicology studies (i.e., rats and monkeys), as well as humans, is due to the lack of mast cells beneath the endothelium of the hepatic vein in these species.

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Section: Discussionmentioning

confidence: 98%

Dog-specific hemorrhagic changes induced by liposomal formulations, in the liver and the gallbladder

et al. 2020

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Section: Discussionmentioning

confidence: 99%

“…Another special feature of the dog liver is the presence of mast cells along the endothelial lining of sublobular and central veins, as well as within the Disse’s spaces (Fujita 1964; Kobayashi et al 1985). Mast cells in the Disse’s spaces have not been documented in any other vertebrate species than the dog (Kobayashi et al, 1985). Interestingly, the mast cells in the Disse’s spaces of dogs have been found to be in close contact with the stellate (Ito) cells, the primary source of collagen in the liver (Kobayashi et al 1985).…”

Section: Discussionmentioning

confidence: 99%

Early Stellate Cell Activation and Veno-occlusive-disease (VOD)–like Hepatotoxicity in Dogs Treated with AR-H047108, an Imidazopyridine Proton Pump Inhibitor

et al. 2008

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Dogs treated with AR-H047108, an imidazopyridine potassium competitive acid blocker (P-CAB), developed clinical signs of hepatic dysfunction as well as morphologically manifest hepatotoxicity in repeat-dose toxicity studies. An investigative one-month study was performed, with interim euthanasia after one and two weeks. A detailed histopathological and immunohistochemical characterization of the liver lesions was conducted, including markers for fibrosis, Kupffer cell activation, apoptosis, and endothelial injury. In addition, hepatic retinoid and procollagen 1alpha2 mRNA levels in livers of dogs treated with AR-H047108 were analyzed. The results showed an early inflammatory process in central veins and centrilobular areas, present after one week of treatment. This inflammatory reaction was paralleled by activation of stellate/Ito cells to myofibroblasts and was associated with sinusoidal and centrivenular fibrosis. The early activation of stellate cells coincided with a significant decrease in retinyl ester levels, and a significant increase in procollagen 1alpha2 mRNA levels, in the liver. At later time points (three and six months), there was marked sinusoidal fibrosis in centrilobular areas, as well as occlusion of central veins resulting from a combination of fibrosis and increased thickness of smooth muscle bundles in the vessel wall. The pattern of lesions suggests a veno-occlusive-disease (VOD)-like scenario, possibly linked to the imidazopyridine chemical structure of the compound facilitated by specific morphological features of the dog liver.

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“…Such a positioning of the mast cell seems to be favorable for the reception of stimulating substances in the blood. In this context, it seems worthy of note that KOBAYASHI et al (1985) described mast cells in the Disse's space in the dog liver as frequently protruding their cytoplasmic processes into sinusoids through endothelial fenestrations.…”

Section: Normal Dog Liversmentioning

confidence: 96%

Canine hepatic vein branches associated with subendothelial mast cells and an adventitial lymphatic plexus.

Takahashi-Iwanaga

Fujita

Takeda

1990

Archives of Histology and Cytology

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Mast cell-Ito cell pairings found in the Disse's spaces in the liver of the beagle dog.

Cited by 9 publications

References 17 publications

Dog-specific hemorrhagic changes induced by liposomal formulations, in the liver and the gallbladder

Dog-specific hemorrhagic changes induced by liposomal formulations, in the liver and the gallbladder

Early Stellate Cell Activation and Veno-occlusive-disease (VOD)–like Hepatotoxicity in Dogs Treated with AR-H047108, an Imidazopyridine Proton Pump Inhibitor

Canine hepatic vein branches associated with subendothelial mast cells and an adventitial lymphatic plexus.

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