Monette, Margaret Mariscal
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The nature and mechanism of action of host-derived molecules termed alarmins or damage-associated molecular patterns (DAMPs) in the inflammatory response remains elusive. The hypothesis in this work states that a soluble histone H1x-like protein, NCAMP-1 functions as an endogenous danger molecule in zebrafish. NCAMP-1 was present in the cytoplasm of different cell types and tissues and was released from immune cells. To identify pathways utilized by NCAMP-1 in cellular binding and activation, its effects were compared to those of ATP, known to act through the ligand-gated ion channel, P2X7 receptor. Binding of either agonist to zebrafish leukocytes initiated intracellular calcium mobilization, pore formation and increased cytotoxic killing. While some of the effects between the two agonists are similar, significant differences in their mechanisms of action were found. Therefore, NCAMP-1 may utilize a unique mechanism of cellular binding and activation in its role as a multi-functional effector molecule and inflammatory mediator.