Effects of tumour necrosis factor α (TNFα) on Mytilus haemocytes: role of stress-activated mitogen-activated protein kinases (MAPKs)

• Published in: Biology of the cell Vol. 98; no. 4; pp. 233 - 244
• Main Authors: Betti, Michele, Ciacci, Caterina, Lorusso, Lucia C., Canonico, Barbara, Falcioni, Tania, Gallo, Gabriella, Canesi, Laura
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2006
• Subjects: Animals; c-Jun N-terminal kinase (JNK); cytokine; Dose-Response Relationship, Drug; Drug Synergism; Enzyme Activation; Flow Cytometry; haemolymph; Hemocytes - drug effects; Marine; Mitogen-Activated Protein Kinases - metabolism; mussel; Mytilus; Mytilus galloprovincialis; p38; Phosphorylation; Protein Kinase Inhibitors - pharmacology; Signal Transduction; STAT1 Transcription Factor - metabolism; Time Factors; Tumor Necrosis Factor-alpha - pharmacology; Tyrosine - metabolism
• ISSN: 0248-4900; 1768-322X
• DOI: 10.1042/BC20050049

Background information. Many studies indicate that innate immunity in invertebrates can be modulated by a cytokine network like in vertebrates. In molluscs, the immune response is carried out by circulating haemocytes and soluble haemolymph factors. In the present study, the effects of heterologous TNFα (tumour necrosis factor α) on cell signalling and function in the haemocytes of the bivalve Mytilus galloprovincialis Lam. were investigated. Results and conclusions. Addition of TNFα in the absence of haemolymph serum [in ASW (artificial sea water)] induced cellular stress, as indicated by lysosomal destabilization, and decreased phagocytosis; on the other hand, in the presence of serum, TNFα did not affect lysosomal stability and even stimulated phagocytosis. TNFα induced rapid phosphorylation of the stress‐activated p38 and JNK (c‐Jun N‐terminal kinase) MAPKs (mitogen‐activated protein kinases); both effects were persistent in ASW but transient in serum. Activation of p38 and JNKs in mediating the effects of TNFα was confirmed by the use of specific MAPK inhibitors. Moreover, flow cytometric analysis indicated that TNFα in the presence of serum induced transient phosphatidylserine exposure on the haemocyte surface, evaluated as annexin V binding; in ASW, the cytokine resulted in a stable increase in the percentage of both annexin‐ and propidium iodide‐positive cells, indicating possible apoptotic/necrotic processes. The results indicate that TNFα can affect the function of bivalve haemocytes through conserved transduction pathways involving stress‐activated MAPKs and suggest that the haemocyte response to the cytokine is influenced by soluble haemolymph components.