title: Release of surface-expressed lactoferrin from polymorphonuclear neutrophils after contact with CD4+ T cells and its modulation on Th1/Th2 cytokine production.
abstract: It is conceivable that a membrane component(s) is transferred from antigen-presenting cells to T cells after antigenic stimulation. However, it is not clear whether a certain membrane component(s) is transferred from polymorphonuclear neturophils (PMN) to T cells for immunomodulation. In the presence study, we cocultured two of the three autologous cells-PMN, CD4+ T, and red blood cells (RBC)-homotypically or heterotypically for 1 h. Spontaneous membrane exchange between autologous PMN-PMN and PMN-CD4+ T but not between CD4+ T-CD4+ T or RBC-CD4+ T was observed with a confocal microscope. Loss of membrane exchange between two paraformaldehyde-fixed cells suggests that mutual membrane exchange is via cell-cell contact. Different combinations of cellular enzyme-linked immunosorbent assay for measuring the binding between fixed cells and biotinylated cell lysates showed the same tendency. To identify the molecule(s) mediating PMN-CD4+ T binding, we compared the banding of biotinylated PMN lysates and the banding of plain PMN lysate probed by biotinylated CD4+ T lysate in 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We found that a 75- to 80-kDa surface-expressed molecule on PMN exists constantly to mediate PMN-CD4+ T binding. Peptide analysis disclosed that the molecule had 99.8% identity with lactoferrin (LF). The expression of LF on system lupus erythematosis (SLE)-PMN is less than normal PMN. PMN-CD4+ T coculture increased LF expression on CD4+ T. Normal PMN and human milk-derived LF suppressed interferon-gamma (IFN-gamma) but enhanced interleukin (IL)-10 production of anti-CD3+anti-CD28-activated, normal CD4+ T. In contrast, coculture of SLE-PMN and autologous CD4+ T suppressed IFN-gamma and IL-10 production. These results suggest that the surface-expressed LF released from PMN after contact with autologous CD4+ T modulated its T helper cell type 1 (Th1)/Th2 cytokine production. Decreased LF expression on SLE-PMN abnormally modulates Th1/Th2 production by CD4+ T cells.
authors.affiliation: Department of Internal Medicine, Buddist Tzu-Chi General Hospital Taipei Branch, Taiwan.
authors.forename: Ko-Jen
authors.initials: KJ
authors.lastname: Li
authors.forename: Ming-Chi
authors.initials: MC
authors.lastname: Lu
authors.forename: Song-Chou
authors.initials: SC
authors.lastname: Hsieh
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Wu
authors.forename: Hsin-Su
authors.initials: HS
authors.lastname: Yu
authors.forename: Chang-Youh
authors.initials: CY
authors.lastname: Tsai
authors.forename: Chia-Li
authors.initials: CL
authors.lastname: Yu
mesh_terms: D000954:Antigens, Surface; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D016022:Case-Control Studies; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000502:physiology; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism* / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology*; D019899:Paracrine Communication; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000954:Antigens, Surface; D007781:Lactoferrin