title: An IgM-kappa rat monoclonal antibody specific for the type 1 sphingosine 1-phosphate G protein-coupled receptor with antagonist and agonist activities.
abstract: Sphingosine 1-phosphate (S1P) type 1G protein-coupled receptors (S1P1 GPCRs) are specific high-affinity transducers for this lipid growth factor and cellular mediator. S1P1 GPCRs are widely-expressed and physiologically critical in the cardiovascular and immune systems. Functional rat monoclonal antibodies (MoAbs) have been generated against human S1P1 GPCRs expressed in rat null-cell transductants to provide bioavailable agents capable of stimulating or suppressing the S1P-S1P1 GPCR axis. The rat IgM-kappa anti-S1P1 GPCR MoAb designated 4B5.2 binds specifically to native human or mouse S1P1 GPCRs in cell membranes, but not to solubilized and denatured S1P1 GPCRs. Specific binding of 32P-S1P to cellular S1P1 GPCRs is not blocked by 4B5.2. T cell chemotactic responses to S1P and S1P suppression of T cell chemotaxis to chemokines both are inhibited selectively by 4B5.2. In contrast, generation of gamma-interferon by stimulated T cells is diminished by 4B5.2 as by S1P. T cell S1P1 GPCR-selective antagonist and agonist effects of 4B5.2 in vivo may alter immune responses as distinctively as the available poly-S1P GPCR-directed pharmacological agents, without the undesirable side-effects attributable to actions of these agents on other S1P GPCRs.
authors.affiliation: Departments of Medicine and Microbiology-Immunology, University of California Medical Center, Room UB8B, 533 Parnassus at 4th Avenue, San Francisco, CA 94143-0711, USA. egoetzl@itsa.ucsf.edu
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Goetzl
authors.forename: Dale
authors.initials: D
authors.lastname: Dembrow
authors.forename: James R
authors.initials: JR
authors.lastname: Van Brocklyn
authors.forename: Markus
authors.initials: M
authors.lastname: Gráler
authors.forename: Mei-Chuan
authors.initials: MC
authors.lastname: Huang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis / Q000276:immunology / Q000502:physiology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D051381:Rats; D049349:Receptors, Lysosphingolipid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018925:Chemokines; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D049349:Receptors, Lysosphingolipid; D007371:Interferon-gamma