Disease relevance of GPR126

• Systemic accumulation of these agents following major injury or sepsis may therefore promote shedding of DREG receptors from circulating leukocytes and impair their recruitment to sites of inflammation [1].
• Objective: To investigate the effect of rice dreg enzymatic hydrolysates as an anti-hypertensive in vivo with spontaneous hypertension rats (SHRs) [2].

High impact information on GPR126

• These results demonstrate that the DREG mAbs define a human lymphocyte homing receptor for PLN HEVs and indicate that this human antigen is homologous to the MEL-14-defined murine lymphocyte homing receptor [3].
• Human neutrophils express high levels of the DREG antigen, whose expression is downregulated after treatment with phorbol myristate acetate, or the chemotactic factors C5a and FMLP [4].
• We show that PPME binding to unactivated neutrophils is mediated primarily by a cation- and DREG antigen-dependent mechanism, whereas activated neutrophil-PPME binding is DREG antigen- and cation-independent, and may be due to the translocation of lysosomal mannose-6-phosphate receptors to the cell surface [4].
• The DREG antibodies offer powerful tools for analyzing the role of homing receptors in human neutrophil-endothelial cell interactions, and also may prove valuable in the clinical assessment of neutrophil activation [4].
• The anti-CD62L mAb (DREG 56) blocked this binding interaction by approximately 60% and P11.4 precipitated CD62L from detergent lysates of PMA-activated Jurkat cells [5].

Biological context of GPR126

• RT-PCR experiments and whole mount in situ hybridization in mice showed that DREG is expressed at high levels in the heart and somite during embryogenesis and in the adult lung [6].
• By surface biotinylation as well as by immunofluorescence analysis we demonstrate that endogenous, highly glycosylated VIGR is expressed on the cell surface of endothelial cells (ECs) upon LPS or thrombin treatment, and inducible expression is mediated by MAP kinases, but not NF-kappaB [7].
• In summary, VIGR represents a novel GPCR of the adhesion family, which is unique in its long extra-cellular domain comprising CUB and PTX-like modules and in its inducibility by LPS and thrombin in a subset of ECs, suggesting an important function in cell-adhesion and potentially links inflammation and coagulation [7].

Anatomical context of GPR126

• When DREG was transiently expressed in mammalian cultured cells, a 35-kD fragment was generated by endogenous proteolytic processing at the conserved GPS domain [6].
• For 14 nonseptic patients, mean monocyte positivity for DREG was reduced from 64% to 40% [1].

Associations of GPR126 with chemical compounds

• The mannose-6-phosphate rich phosphomannan (PPME) binds human lymphocytes via the DREG antigen [4].
• Cross-linking of L-selectin with DREG and 2 degrees antibody did not trigger production of H2O2 by itself but significantly enhanced the subsequent response to two soluble activating agents; the formyl peptide formyl-Met-Leu-Phe (fMLP) and tumor necrosis factor (TNF) [8].

Other interactions of GPR126

• GPR127 has one EGF domain while GPR126 and GPR128 do not contain domains that are readily recognized in other proteins beyond the GPS domain [9].

Analytical, diagnostic and therapeutic context of GPR126

• To test this hypothesis, we have analyzed the expression of DREG receptors on neutrophils and monocytes from 25 patients admitted to the Surgical Intensive Care Unit [1].
• Conclusions: The present study indicated the inhibitory peptides from rice dreg hydrolysate had significant antihypertensive action and no other side effects by oral administration in SHR [2].

References