Soluble form of the triggering receptor expressed on myeloid cells 1: An anti-inflammatory mediator?

Excerpt

Although the quality of the immediate innate immune response is a determinant in the fight against invasive pathogens, its exaggerated amplification may be deleterious and lead to septic shock. One of the pathways leading to such an intensification of the initial and appropriate inflammatory response involves the triggering receptor expressed on myeloid cells (TREM) 1. TREM-1 belongs to a family related to natural killer cell receptors and is present on the surface of neutrophils and mature monocytes [1]. Its expression is upregulated during infection but not during inflammation of noninfectious origin [2]. Upon stimulation by its as yet unknown ligand TREM-1 activates a downstream signal with the help of an accessory protein called DAP12 (or KARAP) leading to cytoskeleton rearrangement, calcium mobilization, and the activation of several transcriptional factors. Indeed, TREM-1 synergizes the effects of the Toll-like receptor ligands 2, 3, and 4 and amplifies the synthesis of many proinflammatory cytokines and chemokines [1]. TREM-1 also promotes an immediate neutrophilic degranulation and the phagocytic respiratory burst [3]. In addition to its presence as a membrane bound form, TREM-1 can also be found as a soluble protein, probably released from the membrane by proteolytic cleavage [4]. The role of this soluble TREM-1 (sTREM-1) as an “anti-inflammatory” agent is becoming understood. …