OBJECTIVETo prepare and identify a polyclonal antibody (pAb) against GPR17, a novel cysteinyl leukotriene receptor.

METHODSRabbits were immunized with KLH-coupled GPR17 peptide to prepare the pAb. The titer of the pAb in rabbit plasma was detected by indirect ELISA, and the specificity of the pAb was tested by antigen blockade. GPR17 tissue distribution was detected by Western blot with the pAb.

RESULTSThe pAb showed a titer as high as 1:16 364,and was not cross-reacted with the antigens of CysLT(1) and CysLT(2) receptors. A higher expression of GPR17 in the rat brain and heart was detected using the newly prepared pAb. The molecular weigh of GPR17 protein was about 43 kD.

CONCLUSIONThe prepared GPR17 pAb has high sensitivity and specificity,and can be used in Western blot for detecting GPR17.

Animals ; Antibodies, Monoclonal ; biosynthesis ; immunology ; Enzyme-Linked Immunosorbent Assay ; Humans ; Rabbits ; Rats ; Receptors, G-Protein-Coupled ; immunology ; Receptors, Leukotriene ; immunology

OBJECTIVE: To observe expression and distribution of histamine H4 receptor in nasal mucosa in normal people and allergic rhinitis patients,and understand role of histamine H4 receptor in allergic rhinitis. METHOD: Select normal people and allergic rhinitis patients each 10, take the nasal mucosa, detect expression and distribution of histamine H4 receptor at proteins and transcription level respectively by immunohistochemical method and RT-PCR, and compared. RESULT: Histamine H4 receptor at proteins and transcription level were found in normal nasal mucosa (25 509 +/- 6 441, 0.42 +/- 0.08), increased significantly in nasal mucosa of allergic rhinitis patients (49 676 +/- 8 541, 0.69 +/- 0.11, P < 0.05), which in structural cells and immune cells. CONCLUSION Histamine H4 receptors exist in normal nasal mucosa, its express significantly enhance, flew histamine H4 receptor may be mediated histamine in pathogenesis of allergic rhinitis ,who is one of the ligands of histamine.
Case-Control Studies ; Humans ; Nasal Mucosa ; immunology ; metabolism ; pathology ; Receptors, G-Protein-Coupled ; metabolism ; Receptors, Histamine ; metabolism ; Receptors, Histamine H4 ; Rhinitis, Allergic, Perennial ; immunology ; metabolism ; pathology

Sphingosine 1-phosphate (S1P) is an important biologically active lysophospholipid that transmits signals through a family of G-protein-coupled receptors (GPCRs) to regulate the vital functions of several types of immune cells. The S1P GPCRs suppress both generation of specialized functional cytokines, such as IFN-gamma and IL-4, and proliferation of T-cells. Although S1P is chemotactic to T cells, B cells, dendritic cells, and natural killer cells, the major effect of S1P on the immune system is the regulation of lymphocyte recirculation and tissue distribution by S1P and S1P1. Chemotactic response of CD4+CD25+ regulatory T cells to S1P is reduced, but its optimal suppressive activities require S1P. FTY720, a new class of immunomodulator, is rapidly phosphorylated by sphingosine kinase 2 in vivo to form the biologically active phosphorylated-FTY720 (FTY720-P), which closely resembles S1P. The FTY720-P is a true agonist for S1P1, S1P3, S1P4, and S1P5, it affects the tissue distribution and functional activity of T cells, B cells, dendritic cells and regulatory T cells. FTY720 were demonstrated to be a hypotoxic, great effective and reversible immunosuppressive efficacy to prevent allograft rejection and treat some autoimmune diseases. In this article, the synthesis and metabolism of S1P, the expression of S1P GPCRs in immune cells, the effect of S1P on immune cells, the drugs targeted to S1P GPCRs and their clinical implications are reviewed.
Fingolimod Hydrochloride ; Humans ; Immunomodulation ; physiology ; Lysophospholipids ; immunology ; physiology ; Propylene Glycols ; metabolism ; Receptors, G-Protein-Coupled ; immunology ; physiology ; Sphingosine ; analogs & derivatives ; immunology ; metabolism ; physiology

Multiple myeloma (MM), considered an incurable hematological malignancy, is characterized by its clonal evolution of malignant plasma cells. Although the application of autologous stem cell transplantation (ASCT) and the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have doubled the median overall survival to eight years, relapsed and refractory diseases are still frequent events in the course of MM. To achieve a durable and deep remission, immunotherapy modalities have been developed for relapsed/refractory multiple myeloma (RRMM). Among these approaches, chimeric antigen receptor (CAR) T-cell therapy is the most promising star, based on the results of previous success in B-cell neoplasms. In this immunotherapy, autologous T cells are engineered to express an artificial receptor which targets a tumor-associated antigen and initiates the T-cell killing procedure. Tisagenlecleucel and Axicabtagene, targeting the CD19 antigen, are the two pacesetters of CAR T-cell products. They were approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). Their development enabled unparalleled efficacy in combating hematopoietic neoplasms. In this review article, we summarize six promising candidate antigens in MM that can be targeted by CARs and discuss some noteworthy studies of the safety profile of current CAR T-cell therapy.
ADP-ribosyl Cyclase 1/immunology* ; B-Cell Maturation Antigen/immunology* ; Humans ; Immunotherapy, Adoptive/methods* ; Multiple Myeloma/therapy* ; Receptors, Chimeric Antigen/immunology* ; Receptors, G-Protein-Coupled/immunology* ; Signaling Lymphocytic Activation Molecule Family/immunology* ; Syndecan-1/immunology* ; T-Lymphocytes/immunology*