Nerve Growth Factor Activates Mast Cells Through the Collaborative Interaction with Lysophosphatidylserine Expressed on the Membrane Surface of Activated Platelets

Abstract

Effect of nerve growth factor (NGF) on platelet-associated mast cell activation was investigated. Although neither NGF alone nor platelets alone induced significant 5-hydroxytriptamine (5-HT) release from rat peritoneal mast cells, marked 5-HT release was detected when costimulated with NGF and calcium ionophore-activated platelets. This response reached maximal levels as early as 5 min after the initiation of the coincubation and was completely blocked by anti-NGF Ab or by an inhibitor for a tyrosine kinase of the trkA NGF receptor. Paraformaldehyde-fixed platelets activated with either calcium ionophore or thrombin exhibited the collaborative ability, suggesting the possible involvement of some membrane molecules expressed on activated platelets in mast cell activation. Because activation of platelets induced expression of phosphatidylserine (PS) and/or lysoPS on membrane surface, and since lysoPS, unlike PS, initiated the NGF-induced 5-HT release, lysoPS expressed on activated platelets may be involved in the mast cell activation. Moreover, intradermal injection of NGF and activated platelets into the rat skin increased local vascular permeability. These findings suggested that NGF collaboratively worked with membrane lysoPS of activated platelets to induce mast cell activation. Thus, NGF released in response to inflammatory stimuli may contribute to mast cell activation in collaboration with locally activated platelets in the process of inflammations and tissue repair.

Neuropeptides Activate Human Mast Cell Degranulation and Chemokine Production

“…This is consistent with observations made by Guhl et al who found that LAD2 production of TNF was only partially NK1R dependent even though LAD2 express mRNA for NK1R and NK2R. 36 Consistent with rodent mast cells, [50][51][52] we have shown that human mast cells express NK1R, NK2R and NK3R on their cell surface and SP may activate human mast cells via one or more of these receptors. However, because the SP-P-T inhibitor only partially blocked SP's effect, SP triggering of mast cells may also involve insertion of the amphiphilic SP molecule into the cell membrane, thus enabling direct activation of G proteins.…”

NADPH Oxidase-dependent Generation of Lysophosphatidylserine Enhances Clearance of Activated and Dying Neutrophils via G2A

“…Lyso-PS Are Abundant Modified PS Species Generated in Neutrophils Stimulated to Activate the NADPH Oxidase-The signaling potential of lyso-PS was first recognized in its description as a potent mast cell secretagogue, and it has subsequently been given signaling roles in other settings (20,21,39,55,56). Here, we have shown that lyso-PS species were generated in vitro and in vivo as major modified PS species in neutrophils stimulated to activate the NADPH oxidase.…”

Lysophospholipids of Different Classes Mobilize Neutrophil Secretory Vesicles and Induce Redundant Signaling through G2A

“…Of note, biological activities, both in vitro and in vivo, have been described previously for lyso-PS and lyso-PE. Lyso-PS has been shown to stimulate calcium flux in ovarian and breast cancer cell lines (48), leukemia cells (42), mast cells (49), and fibroblasts (43), but in other instances has had no biological effect when compared with lyso-PC (7,42). Although a lyso-PS-specific GPR34 has been recently identified in mast cells (50), its limited tissue distribution makes it unlikely to have mediated many effects previously reported for lyso-PS.…”