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

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.

Intercellular transfer of HLA‐G: its potential in cancer immunology

“…First, inhibition of the intercellular transfer of HLA‐G could be obtained by various inhibitors involved in impairing the formation and production of trogocytosis, exosomes and TnTs. The process of trogocytosis was reported to be inhibited by inhibitors of mitogen‐activated protein kinase (PD98059) and protein kinase C (Rottlerin) . The biogenesis and release of exosomes could be impaired by dimethyl amiloride and inactivation of the small GTP‐binding protein ARF6, respectively .…”

“…The process of trogocytosis was reported to be inhibited by inhibitors of mitogen-activated protein kinase (PD98059) and protein kinase C (Rottlerin). 69 The biogenesis and release of exosomes could be impaired by dimethyl amiloride and inactivation of the small GTPbinding protein ARF6, respectively. 70,71 Additionally, the formation of TnTs could be inhibited by mTOR signalling inhibitors metformin and everolimus, and cytoskeletal inhibitors docetaxel and latrunculin A as previously reported.…”

Neutrophils kill the parasite Trichomonas vaginalis using trogocytosis

“…Recently, PMNs have been shown to perform trogocytosis (trogo = to nibble), a mechanism by which fragments, or “bites,” are taken from one cell by a neighboring cell [ 34 , 35 , 36 ]. Trogocytosis has been described as a way for immune cells to exchange membrane proteins [ 34 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ] and as a process recently shown to be exploited by intracellular bacteria for cell–cell transfer [ 44 , 45 ]. Parasitic amoebae have also been shown to injure or kill host cells via trogocytosis [ 46 , 47 , 48 ].…”

Monitoring Cell Proliferation by Dye Dilution: Considerations for Probe Selection

“…4B). When such an increase is seen (e.g., [3]), it is important to determine whether it is dye-related (e.g., transfer of free dye between labeled and unlabeled cells) or cell-related (e.g., cytoplasmic transfer via membrane “podia” or tunneling nanotubes [46,47]), transfer of labeled membrane via trogocytosis [48–50], or uptake of extracellular vesicles carrying labeled proteins or membrane [24]. Although U937s and other tumor cell lines are known to undergo self-trogocytosis [48], the rapid and unusually large intensity increase seen for seen for CYY compared with CTV and other dyes studied suggested that the “dye transfer” shown in Fig.…”