Splenectomy‐reduced hepatic injury induced by ischemia/reperfusion in the rat

Okuaki, Yasushi; Miyazaki, Hiroshi; Zeniya, Mikio; Ishikawa, Tomohisa; Ohkawa, Yasuhiko; Tsuno, Shinichi; Sakaguchi, Masami; Hara, Masaki; Takahashi, Hiroki; Toda, Gotaro

doi:10.1111/j.1600-0676.1996.tb00726.x

Cited by 62 publications

(37 citation statements)

References 22 publications

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“…In addition, T cell-mediated effects could be amplified by other ectopic sites such as the spleen. In support of this hypothesis, a recent report by Okuaki et al (32) has demonstrated reduction of neutrophil infiltration and attenuation of I/R injury in splenectomized animals compared with controls. In the context of this present study, data suggest that Th17 cells at distant sites to the liver such as the spleen may be involved in the inflammatory process.…”

Section: Role Of Kupffer Cells and The Splenic Lymphocytes In Hepaticsupporting

confidence: 54%

Role of IL-17A in Neutrophil Recruitment and Hepatic Injury after Warm Ischemia–Reperfusion Mice

Kono

Fujii

Ogiku

et al. 2011

The Journal of Immunology

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Recent evidence suggests that IL-17A regulates neutrophil-dependent organ injury. Accordingly, the purpose of this study was to determine the role of IL-17A in neutrophil recruitment after ischemia–reperfusion (I/R) and in subsequent liver injury. Two mouse models including wild-type and IL-17A knockout mice were evaluated for I/R injury. The medial largest lobe of the liver was clamped for 90 min. In another set of experiments, recombinant mouse (rm)IL-17A homodimer or rmIL-17A/F heterodimer were administered to knockout mice before I/R, and liver injury was investigated. Isolated Kupffer cells were incubated with rmIL-17A or rmIL-17F, and production of TNF-α was measured. Studies evaluating the extent of liver injury as measured by serum transaminase levels demonstrated similar levels in the acute phase (6 h) in these two models. In contrast, in the subacute phase (20 h) after I/R, both serum transaminase levels and percent of hepatic necrosis were significantly reduced in the knockout mice compared with the wild-type mice. This reduction in liver injury seen in the knockout mice was associated with suppression of chemokine and adhesion molecule expression and reduction in infiltration of neutrophils into the liver. Administration of rmIL-17A homodimer, but not IL-17A/F heterodimer, increased liver injury in the subacute phase of I/R in KO mice. TNF-α production by isolated Kupffer cells increased significantly in the cells incubated with rmIL-17A compared with rmIL-17F. These results indicate that IL-17A is a key regulator in initiating neutrophil-induced inflammatory responses and hepatic injury in the subacute phase after reperfusion.

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Section: Role Of Kupffer Cells and The Splenic Lymphocytes In Hepaticsupporting

confidence: 54%

Role of IL-17A in Neutrophil Recruitment and Hepatic Injury after Warm Ischemia–Reperfusion Mice

Kono

Fujii

Ogiku

et al. 2011

The Journal of Immunology

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“…injection was superior suggesting that the splenic actions of these cells were important for the therapeutic benefit of this treatment [62]. Splenectomy significantly reduces ischemic injury in multiple organ systems including liver [63], GI tract [64], and kidney [65]. Recent results in our lab show that splenectomy prior to stroke reduces infarct volume by 80% [66]; similar to levels of protection seen in HUCBC therapies [61].…”

Section: The Role Of the Peripheral Lymphoid Organs In Strokesupporting

confidence: 73%

Implications of Immune System in Stroke for Novel Therapeutic Approaches

Hall

Pennypacker

2010

Transl. Stroke Res.

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Each year, approximately 795,000 people suffer a new or recurrent stroke. About 610,000 of these are first attacks, and 185,000 are recurrent attacks. Currently, the only FDA approved treatment for ischemic stroke is the thrombolytic recombinant tissue plasminogen activator (Alteplase), which must be given within 4.5 h of stroke onset. Beyond this time, apoptotic and inflammatory processes greatly diminish the therapeutic benefits of current treatments. While there have been many experimental treatments for stroke that showed promising preclinical efficacy, these treatments have failed to show efficacy in clinical trials. In many of these cases, the preclinical animal studies did not model the clinical setting effectively. The injury that occurs following stroke is a dynamic process. To effectively treat stroke patients at clinically relevant timepoints, it is imperative to understand both the humeral and cell-mediated phenomena that occur throughout the body in response to ischemic injury over time. Promising experimental therapeutics designed to be given 1 to 2 days following stroke require both neuroprotective and anti-inflammatory properties in order to be efficacious.

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“…For example, it has been shown that rats splenectomized just prior to an ischemic insult to the liver demonstrated a reduction not only in neutrophil accumulation but also in biochemical and histological parameters of liver injury following 24 h of reperfusion. 24 Activation of lymphocytes at ectopic sites would be unaffected by FTY720 pretreatment, which could possibly account for the observed lack of effect on neutrophil recruitment. Additionally, the lymphocytosis observed in the untreated control group at 24 h of hepatic reperfusion may lend support to the notion that a systemic inflammatory response contributes to this process.…”

Section: Discussionmentioning

confidence: 95%