THERMAL INJURY-INDUCED PRIMING EFFECT OF NEUTROPHIL IS TNF-α AND P38 DEPENDENT

Abstract

Priming response of neutrophil in clinical-related conditions and its mechanism has not been clarified. This study is to determine if thermal injury-induced priming effect of neutrophil is TNF-alpha and p38 dependent. In Experiment 1, bone marrow neutrophil of wild-type (WT) mice and TNF receptor superfamily, member 1A (Tnfrsf1a-/-) mice were harvested and treated with TNF-alpha, platelet activating factor (PAF) first, then with or without N-formyl-Met-Leu-Phe (fMLP). Reactive oxygen species (ROS) production and p38 phosphorylation were evaluated. In Experiment 2, ROS of neutrophil from WT and Tnfrsf1a-/- mice at 3 or 15 h after thermal injury with or without fMLP treatment were assayed. In Experiment 3, p38 and p44/42 phosphorylation, CXCR2 and macrophage inflammatory protein-2 expression, apoptotic ratio, and activating protein-1 (AP-1) and nuclear factor-kappa B (NF-kappaB) activation of neutrophil from WT and Tnfrsf1a-/- mice at 3 h after thermal injury were tested. FMLP treatment after TNF-alpha or PAF incubation of neutrophil increased ROS of PAF-treated but not TNF-alpha-treated neutrophil. PAF treatment increased ROS of neutrophil in WT and Tnfrsf1a-/- mice. FMLP increased ROS of neutrophil of WT mice at 3 h after thermal but not that of Tnfrsf1a-/- mice. TNF-alpha and PAF increased p38 phosphorylation of neutrophil in WT but not that in Tnfrsf1a-/- mice. Thermal injury increased p38 phosphorylation, NF-kappaB activation, and decreased apoptosis of neutrophil at 3 h after thermal injury in WT but not in Tnfrsf1a-/- mice. Thermal injury also induced AP-1 activation and ROS production on neutrophil at 3 and 15 h after thermal injury, respectively, in WT and Tnfrsf1a-/- mice. Collectively, fMLP stimulates ROS of neutrophil through TNF-alpha signaling; PAF stimulates that of neutrophil through both TNF-alpha-dependent and TNF-alpha-independent pathway. Thermal injury induces a TNF-alpha-dependent priming effect and a TNF-alpha-independent activation effect on neutrophil at 3 and 15 h after thermal injury, respectively. NF-kappaB signaling pathway plays an important role in neutrophil activation. Thermal injury also induces TNF-alpha-dependent delay apoptosis and TNF-alpha-independent AP-1 activation of neutrophil at 3 h after thermal injury. Taken together with the TNF-alpha-dependent p38 and NF-kappaB activation in primed neutrophil, we conclude that thermal injury-induced priming effect of polymorphonuclear neutrophil is TNF-alpha and p38 dependent.

Association of TNF-α Gene Promoter Polymorphisms With Susceptibility of Cervical Cancer in Southwest China

“…20 A moderate TNF-α level is necessary to maintain cell in-setting and to prevent certain diseases through regulating immune response. 21 However, excessive TNF-α due to pathological conditions is associated with autoimmune diseases, infectious diseases, and malignant tumors. 22 In the present study, the level of TNF-α was higher in cervical cancer patients than in healthy controls.…”

Early infection during burn-induced inflammatory response results in increased mortality and p38-mediated neutrophil dysfunction

“…Functional changes in neutrophils are influenced by downstream effects on NF-B by mitogenactivated protein kinases (MAPK) such as p38, ERK, and AKT. Burn injury-induced priming of neutrophils was shown to be p38 dependent (6), while ERK activation during thermal injury was associated with enhanced neutrophil O 2 production (13). Additionally, decreased neutrophil apoptosis and increased oxidative burst is associated with elevated levels of activated AKT (7,17).…”

“…Infections in thermally injured patients are often associated with opportunistic organisms such as Pseudomonas aeruginosa (PA), Staphylococcus epidermidis, and Staphylococcus aureus (26,27,41). Studies suggest that blunted bacterial clearance allows for organism propagation in the burn-injured host (12), possibly due to alterations in neutrophil and macrophage production of reactive oxygen species (6,24).…”

The Inflammatory Cytokine IL-21 is Expressed by Splenic Neutrophils in Response to Transplantation of Allogeneic Cells

“…Although they have been traditionally considered as being critical for the elimination of toxins, bacteria, other organisms and foreign bodies [4][5][6], they also have important inflammatory roles in thermal injury [7], ischemia reperfusion [8], a number of immune related disorders [9][10] and hyperacute solid organ transplant rejection [11]. Depending on the experimental or clinical situation, neutrophils have been reported to secrete IL-8 [12], IL-18 [13], IL-17 [2,[6][7][8] and IFNγ [14]. Although, per cell, neutrophils produce much less cytokine protein than monocytes or lymphocytes [2,15], they are more numerous and may be a major cell identified in inflammatory reactions.…”