title: High glucose concentration impairs ATP outflow and immunoglobulin production by human peripheral B lymphocytes: involvement of P2X7 receptor.
abstract: OBJECTIVE
  Patients with diabetes are more prone to bacterial infections mostly due to hyperglycemia-induced suppression of immune cells function. B lymphocytes by secreting antibodies inhibit microbial replication, but the impact of high glucose concentration on humoral immune response is not fully resolved. The aim of this work was to investigate the effect of high glucose concentration on B cells response to stimulation with a bacterial antigen and autocrine regulation.
  
  
  METHODS
  Purified human peripheral blood B cells were cultured at different glucose concentrations and stimulated in vitro with Staphylococcus aureus Cowan I (SAC) plus IL-2. B cells proliferation, differentiation and IgM expression were analyzed by flow cytometry. B cell ATP release and involvement of P2 purinergic receptors in regulation of IgM secretion was assessed.
  
  
  RESULTS
  B cells cultured at 25 mM glucose in response to SAC stimulation released significantly less (≈ 55%) IgM comparing to cells maintained in 5mM glucose. Under resting and stimulatory conditions B cells released significant quantities of ATP to the culture media, but ATP level decreased when B cells were maintain in high glucose. SAC-induced B cell IgM release was totally blocked by highly selective antagonist (Az11645373) of P2X7 receptor. IgM secretion increased in the presence of potent P2X7 receptor agonist (BzATP), but this effect was abolished by high glucose concentration.
  
  
  CONCLUSIONS
  High glucose concentration impairs B cell function by suppression of P2X7 receptor-dependent IgM release in response to in vitro bacterial antigen stimulation. This alteration may greatly contribute to the impaired humoral immune response in diabetics.
authors.affiliation: Department of Molecular Medicine, Medical University of Gdansk, 80-211 Gdansk, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Sakowicz-Burkiewicz
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kocbuch
authors.forename: Marzena
authors.initials: M
authors.lastname: Grden
authors.forename: Izabela
authors.initials: I
authors.lastname: Maciejewska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Szutowicz
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Pawelczyk
mesh_terms: D000255:Adenosine Triphosphate / Q000276:immunology* / Q000378:metabolism; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D048909:Diabetes Complications / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005260:Female; D005947:Glucose / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D056724:Immunity, Humoral / Q000187:drug effects; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology*; D007239:Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008297:Male; D058920:Purinergic P2X Receptor Antagonists / Q000276:immunology / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000276:immunology / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C516674:AZ 11645373; D007075:Immunoglobulin M; D058920:Purinergic P2X Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D013844:Thiazoles; D000255:Adenosine Triphosphate; D005947:Glucose