Ulvan Activates Chicken Heterophils and Monocytes Through Toll-Like Receptor 2 and Toll-Like Receptor 4

Responsiveness to invasive pathogens, clearance via the inflammatory response, and activation of appropriate acquired responses are all coordinated by innate host defenses. Toll-like receptor (TLR) ligands are potent immune-modulators with profound effects on the generation of adaptive immune responses. This property is being exploited in TLR-based vaccines and therapeutic agents in chickens. However, for administering the TLR agonist, all previous studies used in ovo, intra-muscular or intra-venous routes that cannot be performed in usual farming conditions, thus highlighting the need for TLR ligands that display systemic immune effects when given orally (per os). Here we have demonstrated that an ulvan extract of Ulva armoricana is able to activate avian heterophils and monocytes in vitro. Using specific inhibitors, we have evidenced that ulvan may be a new ligand for TLR2 and TLR4; and that they regulate heterophil activation in slightly different manner. Moreover, activation of heterophils as well as of monocytes leads to release pro-inflammatory cytokines, including interleukin1-β, interferon α and interferon γ, through pathways that we partly identified. Finally, when given per os to animals ulvan induces heterophils and monocytes to be activated in vivo thus leading to a transient release of pro-inflammatory cytokines with plasma concentrations returning toward baseline levels at day 3

The arachidonic acid-LTB4-BLT2 pathway enhances human B-CLL aggressiveness.

International audienceDeregulation of the oxidative cascade of poly-unsaturated fatty acids (PUFAs) has been associated with several cancers, including chronic lymphocytic leukemia (B-CLL). Leukotriene B4 (LTB4), a metabolite of arachidonic acid (AA), is produced by B-CLL and contributes to their survival. The aim of the present study was to analyze the activity of the oxidative cascade of PUFAs in B-CLL. Purified B cells from patients and normal B CD5 positive cells were subjected to flow cytometry, Western-blot and RT-qPCR analyses. LTB4 plasma and intracellular concentrations were determined by ELISA. Our results showed that aggressive B-CLL tumor cells, i.e. cells with an annual proliferation index above 2, over-expressed calcium-dependent and calcium-independent phospholipases A2 (cPLA2-alpha and iPLA2-beta, respectively), 5-lipoxygenase (5LOX) and leukotriene A4 hydroxylase (LTA4H). Intracellular LTB4 levels were lower in the most aggressive cells than in cells with a smaller proliferation index, despite equivalent plasma levels, and lower expression of cytochrome P450 4F3A (CYP4F3A), one major enzyme involved in LTB4 inactivation. Since BLT2, a LTB4 membrane receptor was also more often expressed on aggressive tumor cells, and since a BLT2 inhibitor significantly impaired B-CLL viability in vitro, we propose that LTB4 was efficiently trapped onto BLT2 present on aggressive tumors, thereby eliciting an autocrine response. Taken together our results demonstrate a major deregulation of the pathway leading to LTB4 synthesis and degradation in B-CLL cells, and provide a framework for understanding how these modifications promote cell survival and proliferation, especially in the most aggressive BCLL

Acute renal dysfunction after cardiac surgery with cardiopulmonary bypass is associated with plasmatic IL6 increase.

International audienceBACKGROUND: Acute renal dysfunction (ARD) is common after cardiac surgery with cardiopulmonary bypass (CPB). CPB results in a sudden systemic inflammatory response. Systemic and local pro-inflammatory cytokines synthesis has been linked with sub-clinical renal injury, especially tubular lesions. Therefore, we sought to assess the systemic synthesis pro-inflammatory cytokines and its association with perioperative ARD after cardiac surgery with CPB. METHODS: Sixty-two patients undergoing cardiac surgery with CPB were prospectively included. Four groups of patients were defined according to blood creatinine increase: no ARD (less than 25% increase), faint ARD (25-50% increase), moderate ARD (50-100% increase), severe ARD (more than 100% increase). RESULTS: Within the 48 post-operative hours was ARD observed as no dysfunction (41.9%), faint (32.2%), moderate (16.1%), severe (9.6%). One patient had to undergo a dialysis. Pre-operative characteristics were homogenous between the four groups excepted the left ventricle ejection fraction. ARD was associated with a low urinary output with high sodium excretion fraction. Significant increase of IL-6 level occurred when patients underwent a severe ARD despite no significant differences for the CRP and TNF-alpha concentrations. CONCLUSION: Severe acute renal dysfunction after cardiac surgery with CPB is associated with a significant increased IL-6 systemic production