Mesenteric lymph drainage alleviates hemorrhagic shock-induced spleen injury and inflammation

Zhang, Hong; Zhai, Jia-Yi; Du, Hui-Bo; Zhang, Limin; Li, Linfeng; Bian, Anqi; Jiang, Lina; Zhao, Zi‐Gang

doi:10.1590/s0102-865020190090000003

Cited by 8 publications

(9 citation statements)

References 28 publications

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“…However, the mechanisms of disorder of cellular immune function induced by hemorrhagic shock are not fully understood. It is widely believed that PHSML reflux due to impaired mesenteric barrier and dysfunctional mesenteric lymph node in the body after hemorrhagic shock is strongly associated with distal tissue damage and decrease host resistance to microbial infection (11,(32)(33)(34). It has been reported that after mesenteric lymph node structure and function are damaged, the Th1/Th2 subsets of CD4 + T cells are dysregulated, and the proliferation and of CD4 + T cells are interrupted, thus leading to immune imbalance in the body (35)(36)(37).…”

Section: Effect Of Tlr2/tlr4-mediated Tipe2 On the Levels Of Cytokine...mentioning

confidence: 99%

TLR2/TLR4-Enhanced TIPE2 Expression Is Involved in Post-Hemorrhagic Shock Mesenteric Lymph-Induced Activation of CD4+T Cells

Jiang

Zhao

et al. 2022

Front. Immunol.

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PurposePost hemorrhagic shock mesenteric lymph (PHSML) return contributes to CD4+ T cell dysfunction, which leads to immune dysfunction and uncontrolled inflammatory response. Tumor necrosis factor α induced protein 8 like-2 (TIPE2) is one of the essential proteins to maintain the immune homeostasis. This study investigated the role of TIPE2 in regulation of CD4+ T lymphocyte function in interaction of PHSML and TLR2/TLR4.MethodsThe splenic CD4+ T cells were isolated from various mice (WT, TLR2-/-, TLR4-/-) by immunomagnetic beads, and stimulated with PHSML, normal lymphatic fluid (NML), respectively. Application of TIPE2-carrying interfering fragments of lentivirus were transfected to WT, TLR4-/-, and TLR2-/- CD4+ T cells, respectively. After interference of TIPE2, they were stimulated with PHSML and NML for the examinations of TIPE2, TLR2, and TLR4 mRNA expressions, proliferation, activation molecules on surface, and cytokine secretion function.ResultsPHSML stimulation significantly upregulated TIPE2, TLR2, and TLR4 mRNA expressions, decreased proliferation, CD25 expression, and IFN-γ secretion, and increased the secretion ability of IL-4 in WT CD4+ T cells. TIPE2 silencing enhanced proliferative capacity, upregulated CD25 expression, and increased IFNγ secretion in CD4+ T cells. PHSML stimulated TLR2-/-CD4+ T or TLR4-/-CD4+ T cells of which TIPE2 were silenced. TLR2 or TLR4 knockout attenuated PHSML-induced CD4+ T cells dysfunction; PHSML stimulation of silent TIPE2-expressing TLR2-/-CD4+ T or TLR4-/-CD4+ T revealed that the coexistence of low TIPE2 expression with lack of TLR2 or TLR4 eliminated this beneficial effect.ConclusionTIPE2 improves the PHSML-mediated CD4+T cells dysfunction by regulating TLR2/TLR4 pathway, providing a new intervention target following hemorrhagic shock-induced immune dysfunction.

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Section: Effect Of Tlr2/tlr4-mediated Tipe2 On the Levels Of Cytokine...mentioning

confidence: 99%

TLR2/TLR4-Enhanced TIPE2 Expression Is Involved in Post-Hemorrhagic Shock Mesenteric Lymph-Induced Activation of CD4+T Cells

Jiang

Zhao

et al. 2022

Front. Immunol.

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“…The congestion and necrosis of the spleen tissue and the aggregation of in ammatory cells were evaluated under an optical microscope. Then the spleen injury scores of mice based on the results of H&E [23] was evaluated by two independent, blinded researchers.…”

Section: Histologymentioning

confidence: 99%

CD28 Monoclonal Antibody Improve Sepsis Mortality by Amending Th17/Treg Balance

Wu¹,

Dai²,

Xie³

et al. 2021

Preprint

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Background: Sepsis is still developing exorbitantly high mortality. In response to microbial molecules, T cell activation plays a crucial role in sepsis’s initial innate immune reactions. The imbalance between CD4+IL-17+ T helper cells (Th17) and CD4+CD25+ regulatory T cells (Treg) participates in sepsis progression. CD28 signaling pathway was essential for the expression of inflammatory cytokines related to Th17, and play a crucial role in the maintenance of Treg. We investigated the correlations of the balance between Th17 and Treg to prognosis in sepsis patients and influence of anti-CD28 antibody on the ratio of Th17 to Treg in sepsis mice.Methods: 60 sepsis patients' baseline conditions were recorded, and the expressions of inflammatory factors in the peripheral blood and levels of procalcitonin (PCT) were detected. Peripheral blood mononuclear cells (PBMCs) were separated, subtypes of T cells and related biomarkers were measured by Fluorescence-activated cell sorting (FACS). Furthermore, the relationship between the above indicators and patients’ condition scoring (APACHEⅡand SOFA) and ICU hospitalization time were analyzed. To investigate effects of CD28 on the balance of Th17 between Treg, anti-CD28 antibody was intraperitoneal administrated to cecal ligation and puncture (CLP) mice. Results: Compared with septic patients who stay in ICU more than 14 days, the Th17/Treg ratio of patients with ICU hospitalization of fewer than 14 days was significantly lower. The sepsis patients with higher expression of CD28 in peripheral blood lymphocytes have lower APACHE II and SOFA scores. Moreover, the expression of CD28 was significantly higher in sepsis patients than that of healthy donors. After administration of CD28 monoclonal antibody, 7-day mortality and clinical score were significantly improved in septic mice, with splenocyte Th17/Treg ratio decreased. CD28 antibody alleviates the expression of pro-inflammatory factors and spleen injury related to apoptosis. Conclusions: Th17/Treg ratio revealed septic patient severity and can be used as a predictor of ICU stay. CD28 monoclonal antibody could improve 7-day mortality of septic mice by decreasing T cell apoptosis and amending the ratio of Th17/Treg.Trial registration: CHEC2019-133, CTR20191855. Registered 27 August 2019

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“…Mice were suffered to acute hemorrhage [7], maintaining mean arterial pressure (MAP) of 40 ± 2 mmHg for 60 minutes, followed by resuscitation with shed whole blood and equal volume of ringer's solution.…”

Section: Hemorrhagic Shock Modelmentioning

confidence: 99%

RAS Equilibrium Involves in Mesenteric Lymph Return-Mediated Acute Kidney Injury in Mice Underwent Acute Hemorrhage

K¹,

Zhang²,

Xie³

et al. 2020

Preprint

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Abstract Background: Previous studies demonstrated renin-angiotensin system (RAS) played vital roles in shock-induced organ injury, and mesenteric lymph return was involved in hemorrhagic shock-induced acute kidney injury (AKI). Nevertheless, whether RAS is involved in PHSML-mediated AKI remains unclear. Therefore, this study investigated the role of RAS in post-hemorrhagic shock mesenteric lymph (PHSML)-induced AKI. Methods: After acute hemorrhage and fluid resuscitation, the mice were treated with mesenteric lymph duct ligation (MLDL) and administrations of angiotensin converting enzyme (ACE) inhibitor enalapril, angiotensin (1-7) (Ang (1-7)), angiotensin II (Ang II) type 1 receptor (AT1R) inhibitor losartan, respectively. In addition, the parts of mice with hemorrhage plus MLDL were treated with Ang II, Mas receptor (MasR) inhibitor A-779, respectively. Meanwhile, the ACE2-/- mice received hemorrhage plus MLDL. At 4 h after resuscitation, the kidneys were harvested for the observation of histomorphology and measurement of ACE, ACE2, AT1R, MasR expressions and Ang II and Ang (1-7) levels.Results: Hemorrhagic shock induced renal tissue injury, increased the ACE and AT1R expressions, decreased the ACE2 and MasR expressions in kidney, accompanied by elevated Ang II and depressed Ang (1-7) in kidney. These adverse effects were partially reversed by MLDL or administrations of enalapril, Ang-(1-7), and losartan, respectively. In addition, the beneficial role of MLDL was reversed by ACE2 deficiency and Ang II or A-779 administrations. Conclusion: MLDL alleviates hemorrhagic shock-induced AKI in mice is related to the equilibrium ACE-AngII-AT1R and ACE2-Ang (1-7)-MasR axis.

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Mesenteric lymph drainage alleviates hemorrhagic shock-induced spleen injury and inflammation

Cited by 8 publications

References 28 publications

TLR2/TLR4-Enhanced TIPE2 Expression Is Involved in Post-Hemorrhagic Shock Mesenteric Lymph-Induced Activation of CD4+T Cells

TLR2/TLR4-Enhanced TIPE2 Expression Is Involved in Post-Hemorrhagic Shock Mesenteric Lymph-Induced Activation of CD4+T Cells

CD28 Monoclonal Antibody Improve Sepsis Mortality by Amending Th17/Treg Balance

RAS Equilibrium Involves in Mesenteric Lymph Return-Mediated Acute Kidney Injury in Mice Underwent Acute Hemorrhage

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