Structure,ligands,and roles of GPR126/ADGRG6 in the development and diseases

Adhesion G protein-coupled receptors(aGPCRs)are the second largest diverse group within the GPCR superfamily,which play critical roles in many physiological and patho-logical processes through cell-cell and cell-extracellular matrix interactions.The adhesion GPCR Adgrg6,also known as GPR126,is one of the better-characterized aGPCRs.GPR126 was previously found to have critical developmental roles in Schwann cell maturation and its mediated myelination in the peripheral nervous system in both zebrafish and mammals.Current studies have extended our understanding of GPR126-mediated roles during develop-ment and in human diseases.In this review,we highlighted these recent advances in GPR126 in expression profile,molecular structure,ligand-receptor interactions,and associated physiological and pathological functions in development and diseases.

Immune mechanism and clinical significance of macrophage to medullary hematopoietic injury of immune-related hematocytopenia patients

Background Immune-related hematocytopenia （IRH） is considered to be related with the production of autoantibody, as well as the activation of humoral immunity which is stimulated by B lymphocyte. This study aimed to observe the levels of various cytokines in the blood serum and the in situ active state of macrophage （Me） in the medullary hematopoietic microenvironment of IRH patients, and to probe into the immune mechanism and clinical significance of Me in hematopoietic cell injury. Methods ELISA is used to detect the IL-4, IL-6, IL-12, IL-17, and IFN-y levels in the peripheral blood serum of 376 patients in pre- and post-therapy. Cytochemistry and cell immunochemistry methods are used to observe the peroxidase （POX）, nonspecific esterase （NSE）, hemosiderin granules, and HLA-DR activity of Me in the bone marrow of patients. Immunofluorescence is used to observe the expression of hemocyte antihuman globulin IgG antibody, lymphocytes CD4 molecule, Me membrane Fcyllreceptor （FcyllR）, mannitose receptor （MR）, IFN-y, ICAM-1, IL-12, and IL-17A and the formation mechanism of antibody-dependent cell-mediated cytotoxicity （ADCC） hematopoietic cell islands （HI） in the medullary hematopoietic microenvironment of patients. Glucocorticoid is used for treatment on the basis of anti-infection therapy, and gamma globulin stoss therapy is used for the appearance of ADCC-type HI or serious Me bloodthirsty phenomenon; if necessary, association of Cyclosporine A （CsA） should be used and chalybeate should be supplemented. Results In the patient group, the levels of IL-4, IL-6, IL-12, IL-17, and IFN-y were increased. After treatment, the cytokine levels gradually became normal. The activated Me in the marrow highly expressed NSE and POX, and Me swallowed more hemosiderin particles, but the iron in the cytoplasm of immature erythrocytes decreased. The activated Me expressed HLA-DR, MR, ICAM-1, IFN-y, and IL-12. For patients with humoral immunity activation and bacterial infection, Me weakly expressed IL-17A but highly expressed FcyIIR, and the phenomenon that ADCC-type HI broke pathological blood corpuscles often occurred; for the cellular immune activation along with virus infection, the white blood count （WBC） significantly reduced, Me weakly expressed FcyIIR, secretory highly expressed IL-17A, and the phenomena that Me adhered to, captured and swallowed blood cell often occurred. After four weeks of anti-infective and immunosuppressive therapy, nuclear apoptosis of Me occurred in the bone marrow of patients, HI and bloodthirsty phenomenon disappeared, and the peripheral blood picture started to improve. Conclusions Me is an important antigen presenting cell in the IRH marrow for hematopoiesis destruction and an immune effector cell of hematopoietic injury; infection can promote the activation of Me, upregulate the impression of immune molecule and receptors, form ADCC HI. aeGravate hematoBoietic iniurv, and accelerate the destruction on hematoDoietic cell.