Evidence for Kupffer cell migration along liver sinusoids, from high-resolution in vivo microscopy

MacPhee, P. J.; Schmidt, Eric E.; Groom, A. C.

doi:10.1152/ajpgi.1992.263.1.g17

Cited by 55 publications

(57 citation statements)

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“…34 Although such mechanisms were not directly tested, the results from the present study support the hypothesis that Kupffer cell activation along hepatic sinusoids may contribute to the development of hepatic microvascular perfusion heterogeneity. 18,19 Kupffer cells are located primarily in periportal regions of the liver lobule, regions that possess smaller and more tortuous sinusoids than those of pericentral regions. 35,36 With these apparent differences, one would have expected a predisposition for periportal regions to possess more extensive perfusion heterogeneity if Kupffer cells were, in fact, contributing to the increased perfusion heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

Initiation of remote hepatic injury in the rat: Interactions between Kupffer cells, tumor necrosis factor-?, and microvascular perfusion

et al. 1999

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Severe trauma may initiate a systemic inflammatory response, which in turn may result in remote organ injury. After limb ischemia/reperfusion (I/R), intravital fluorescence microscopy was applied to the livers of normotensive rats to investigate the initiation of remote injury to the liver. Additionally, we determined whether Kupffer cell activation and tumor necrosis factor-␣ (TNF-␣) were involved, via perfusion deficits, in such injury. TNF-␣, measured by immunoassay, peaked at 30 minutes of reperfusion, but returned to baseline within 60 minutes. Limb I/R resulted in significant increases to global hepatocellular injury measured by alanine transaminase (ALT) and lethal hepatocyte injury as seen with intravital fluorescence microscopy. Although the number of perfused sinusoids went unchanged, a significantly augmented perfusion heterogeneity was measured. After 1.5 hours of reperfusion, both TNF-␣ and Kupffer cells were shown to contribute to global hepatocellular injury (e.g., ALT). After 3 hours, TNF-␣ was no longer essential for this injury, suggesting that some other mechanism(s) activated Kupffer cells and initiated hepatocellular injury. Using propidium iodide and fluorescence microscopy, we found that both TNF-␣ and Kupffer cell activation were necessary to drive hepatocytes toward lethal injury. No additional benefits were observed with a combination of TNF-␣ inhibition and Kupffer cell suppression. These results not only implicate both Kupffer cells and TNF-␣ in the initiation of remote hepatic injury, but suggest that sinusoidal perfusion deficits are not essential for the initiation of such injury. Other mechanism(s) are likely involved in the pathogenesis of remote hepatic parenchymal injury. (HEPATOLOGY 1999;30:137-142.)

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Section: Discussionmentioning

confidence: 99%

Initiation of remote hepatic injury in the rat: Interactions between Kupffer cells, tumor necrosis factor-?, and microvascular perfusion

et al. 1999

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“…A key difference between KC and DC is that the latter acquire Ag in peripheral tissues in an immature differentiation state, migrate to local lymphoid tissue, and must then mature before stimulating naive T cells. In contrast, KC are not known to migrate out of the liver, and could potentially acquire and present Ag locally (4,5). In experimental models, the hepatocytes themselves can directly present Ag to naive CD8 ϩ T cells (6,7).…”

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Local Intrahepatic CD8+ T Cell Activation by a Non-Self- Antigen Results in Full Functional Differentiation

Wuensch¹,

Pierce

Crispe³

2006

The Journal of Immunology

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The response of T cells to liver Ags sometimes results in immune tolerance. This has been proposed to result from local, intrahepatic priming, while the expression of the same Ag in liver-draining lymph nodes is believed to result in effective immunity. We tested this model, using an exogenous model Ag expressed only in hepatocytes, due to infection with an adeno-associated virus vector. T cell activation was exclusively intrahepatic, yet in contrast to the predictions of the current model, this resulted in clonal expansion, IFN-γ synthesis, and cytotoxic effector function. Local activation of naive CD8+ T cells can therefore cause full CD8+ T cell activation, and hepatocellular presentation cannot be used to explain the failure of CTL effector function against some liver pathogens such as hepatitis C.

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“…5 They move along sinusoids, scavenge degenerated cells, macromolecules and microorganisms and function as antigen-presenting cells. 4,6,7 By virtue of these capacities and their privileged location within the circulation, KCs form the first line of defense against disseminating colorectal tumor cells. 8 Their role in controlling hepatic metastasis in vivo has been demonstrated by their capacity to kill tumor cells in vitro.…”

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Interactions between rat colon carcinoma cells and Kupffer cells during the onset of hepatic metastasis

Timmers

Vekemans

Vermijlen³

et al. 2004

Intl Journal of Cancer

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Liver sinusoids harbor populations of 2 important types of immunocompetent cells, Kupffer cells (KCsColon cancer is one of the most common cancers in the Western world. 1 Metastases to the liver, a common event in cancer patients, is an important cause of death, and the rate of metastasis generally determines survival time. 2,3 The growth and development of metastasis involve a cascade of tumor-host cell interactions.The first vascular bed encountered by blood-borne tumor cells from the gastrointestinal tract is in the liver, in the sinusoids of which they encounter 2 immunocompetent cells, Kupffer cells (KCs) and natural killer (NK) cells. 4,5 KCs represent the largest macrophage population in the body. 5 They move along sinusoids, scavenge degenerated cells, macromolecules and microorganisms and function as antigen-presenting cells. 4,6,7 By virtue of these capacities and their privileged location within the circulation, KCs form the first line of defense against disseminating colorectal tumor cells. 8 Their role in controlling hepatic metastasis in vivo has been demonstrated by their capacity to kill tumor cells in vitro. 9 -13 It has been shown that binding to tumor cells is necessary for effective killing in vitro, 14 -16 which is accomplished by a variety of mechanisms, including phagocytosis and the release of proteinases, tumor necrosis factor and oxygen metabolites. 4,17,18 The role of KCs in controlling metastasis has been demonstrated at late stages of metastasis (3 weeks); metastasis is enhanced by selectively eliminating KCs and reduced by stimulating them. 8,19 -22 Whether or not this effect can also be observed during the early stages of metastasis has not been reported yet.Liver 32 and the receptor-mediated pathway (members of the TNF family). 33 Both KCs and liver NK cells belong to the innate immune system and are often observed in close contact with each other. 24,27 It is supposed that these cells affect the growth of liver metastases only if they interact with incoming tumor cells shortly after their arrival in the liver (ϳ 24 hr) because later on the natural host defenses may be incapable of limiting metastasis due to the rapid proliferation of the cancer cell population, angiogenesis and weakened host defenses. Synergism between KCs and NK cells in the elimination of tumor cells has been postulated in vivo 34 and illustrated in vitro. 12 However, most studies describing the in situ KC-tumor cell interactions focused on events occurring 2-3 weeks after tumor cell inoculation, 20,22,34,35 and only a few studies examined the early stages of hepatic metastases (Ͻ 24 hr). 36,37 Routine microscopic methods are not optimal for studying early hepatic metastasis because they require thin sections, low sampling volumes, complicated preparation methods and immunohistochemical procedures. 38 In contrast, confocal laser scanning microscopy (CLSM) enables the study of large sample volumes and sections 50 -100 m thick, facilitating investigation of rare cellular events such as the occurrence of tumor...

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Evidence for Kupffer cell migration along liver sinusoids, from high-resolution in vivo microscopy

Cited by 55 publications

References 0 publications

Initiation of remote hepatic injury in the rat: Interactions between Kupffer cells, tumor necrosis factor-?, and microvascular perfusion

Initiation of remote hepatic injury in the rat: Interactions between Kupffer cells, tumor necrosis factor-?, and microvascular perfusion

Local Intrahepatic CD8+ T Cell Activation by a Non-Self- Antigen Results in Full Functional Differentiation

Interactions between rat colon carcinoma cells and Kupffer cells during the onset of hepatic metastasis

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