Membrane Transfer from Mononuclear Cells to Polymorphonuclear Neutrophils Transduces Cell Survival and Activation Signals in the Recipient Cells via Anti-Extrinsic Apoptotic and MAP Kinase Signaling Pathways
Journal
PloS one
Journal Volume
11
Journal Issue
6
Pages
e0156262
Date Issued
2016-06-03
Abstract
The biological significance of membrane transfer (trogocytosis) between polymorphonuclear neutrophils (PMNs) and mononuclear cells (MNCs) remains unclear. We investigated the biological/immunological effects and molecular basis of trogocytosis among various immune cells in healthy individuals and patients with active systemic lupus erythematosus (SLE). By flow cytometry, we determined that molecules in the immunological synapse, including HLA class-I and-II, CD11b and LFA-1, along with CXCR1, are exchanged among autologous PMNs, CD4+ T cells, and U937 cells (monocytes) after cell-cell contact. Small interfering RNA knockdown of the integrin adhesion molecule CD11a in U937 unexpectedly enhanced the level of total membrane transfer from U937 to PMN cells. Functionally, phagocytosis and IL-8 production by PMNs were enhanced after co-culture with T cells. Total membrane transfer from CD4+ T to PMNs delayed PMN apoptosis by suppressing the extrinsic apoptotic molecules, BAX, MYC and caspase 8. This enhancement of activities of PMNs by T cells was found to be mediated via p38- and P44/42-Akt-MAP kinase pathways and inhibited by the actin-polymerization inhibitor, latrunculin B, the clathrin inhibitor, Pitstop-2, and human immunoglobulin G, but not by the caveolin inhibitor, methyl-β-cyclodextrin. In addition, membrane transfer from PMNs enhanced IL-2 production by recipient anti-CD3/anti-CD28 activated MNCs, and this was suppressed by inhibitors of mitogen-activated protein kinase (PD98059) and protein kinase C (Rottlerin). Of clinical significance, decreased total membrane transfer from PMNs to MNCs in patients with active SLE suppressed mononuclear IL-2 production. In conclusion, membrane transfer from MNCs to PMNs, mainly at the immunological synapse, transduces survival and activation signals to enhance PMN functions and is dependent on actin polymerization, clathrin activation, and Fcγ receptors, while membrane transfer from PMNs to MNCs depends on MAP kinase and PKC signaling. Defective membrane transfer from PMNs to MNCs in patients with active systemic lupus erythematous suppressed activated mononuclear IL-2 production.
Subjects
SURFACE-EXPRESSED LACTOFERRIN; DELAYED-TYPE HYPERSENSITIVITY; INVIVO IMMUNE-RESPONSE; RED-BLOOD-CELLS; MHC CLASS-II; T-CELLS; SELECTIVE DEPLETION; MONOCLONAL-ANTIBODY; RP-3 TREATMENT; INTERCELLULAR TRANSFER
SDGs
Other Subjects
caspase 8; CD11b antigen; CD28 antigen; CD3 antigen; chemokine receptor CXCR1; clathrin; Fc receptor; HLA antigen class 1; HLA antigen class 2; interleukin 2; interleukin 8; lymphocyte function associated antigen 1; mitogen activated protein kinase; mitogen activated protein kinase 3; mitogen activated protein kinase p38; Myc protein; protein Bax; protein kinase B; protein kinase C; 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; CD11b antigen; chemokine receptor CXCR1; flavonoid; fused heterocyclic rings; immunoglobulin G; interleukin 2; latrunculin B; lymphocyte function associated antigen 1; mitogen activated protein kinase; pitstop 2; sulfonamide; thiazolidine derivative; actin polymerization; apoptosis; Article; CD4+ T lymphocyte; cell contact; cell survival; controlled study; cytokine production; enzyme activation; enzyme activity; flow cytometry; human; human cell; immunological synapse; intracellular signaling; membrane biology; membrane transport; mononuclear cell; neutrophil; phagocytosis; systemic lupus erythematosus; trogocytosis; U937 cell line; apoptosis; cell survival; drug effects; electroporation; enzyme linked immunosorbent assay; metabolism; mononuclear cell; neutrophil; physiology; signal transduction; U-937 cell line; Western blotting; Antigens, CD11b; Apoptosis; Blotting, Western; Bridged Bicyclo Compounds, Heterocyclic; CD4-Positive T-Lymphocytes; Cell Survival; Electroporation; Enzyme-Linked Immunosorbent Assay; Flavonoids; Humans; Immunoglobulin G; Interleukin-2; Leukocytes, Mononuclear; Lymphocyte Function-Associated Antigen-1; Mitogen-Activated Protein Kinases; Neutrophils; Phagocytosis; Receptors, Interleukin-8A; Signal Transduction; Sulfonamides; Thiazolidines; U937 Cells
Publisher
PUBLIC LIBRARY SCIENCE
Type
journal article