Glutamate induces neutrophil cell migration by activating class I metabotropic glutamate receptors

Abstract

Leukocytes are recruited at the site of infection or injury as a part of the innate immune system, and play a very critical role in fighting the invading microorganisms and/or healing wounds. Neutrophils are the most abundant leukocytes in healthy humans and are the principal cell types that arrive at the target site in the initial phase of this process. Previous studies from our laboratory have shown that the amino acid glutamate is a novel chemotaxis-inducing factor for human neutrophils. In this report, we provide evidences that clearly demonstrate that the glutamate-induced neutrophil cell migration activity is mediated by the class I metabotropic glutamate receptors. Our results further show that a specific integrin β2 (ITG β2) receptor, namely LFA1 (α(L)β(2)) is activated upon glutamate treatment and is required for further downstream signaling events leading to increased migration of human neutrophil cells. Following glutamate stimulation, LFA1 is phosphorylated by the Src Kinase Lck at the Y735 residue, which triggers a downstream signaling cascade leading to activation of PI3K, Syk, Vav and finally the Rho family GTPase, Rac2. Interestingly, glutamate was previously found to be present in elevated levels in wound fluid. Furthermore, glutamate level was also found to go up following inflammation. Taken together, our study suggests a novel mode of neutrophil recruitment to the target site following an infection or injury.

Increased mast cell degranulation and co-localization of mast cells with the NMDA receptor-1 during healing after Achilles tendon rupture

“…To the best of our knowledge, it has not been shown previously that MCs can express such receptors, although there is limited evidence that MCs may respond to glutamate receptor antagonists (Hamasato et al 2013). However, it is known from previous studies that various other types of immune cells, e.g., neutrophils, can express various glutamate receptors (Gupta et al 2013) and the present study thus introduces the MC as a novel cell type potentially having the ability to respond to glutamate. The potential consequences of induced NMDAR1 expression in the MCs of the ruptured tendon are not clear at present.…”

Functional weight-bearing mobilization after Achilles tendon rupture enhances early healing response: a single-blinded randomized controlled trial

“…1–6 weeks) [2]. Glutamate is known to be a chemotaxis-inducing factor for human neutrophils, and glutamate has demonstrated beneficial effects on both mucosal and epidermal wound healing [10, 14, 21]. …”

Some cross-talks between immune cells and epilepsy should not be forgotten

“…These anti-peripheral GluR3 Abs may encounter cerebral GluR3, and thereby interfere the signaling pathway and survival of neuron and glial cells [28]. Other crosstalks between CNS and peripheral glutamate systems are mainly through modulating immune response [30,31] and releasing glutamate, which may lead to endothelial barrier dysfunction [32] and neuronal damage [33]. Non-significant evidence has presented the relationship of other glutamate receptors with epilepsy.…”