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.

Lactoferrin Acts as an Alarmin to Promote the Recruitment and Activation of APCs and Antigen-Specific Immune Responses

“…Furthermore, hLF shares only 68% sequence with its bovine counterpart (21, 34 -36). Therefore, our results may have more relevance for understanding the effect(s) of lactoferrin on human immune cells and immunity than those studies in which the bovine lactoferrin was used (37)(38)(39)(40).…”

Contribution of Neutrophils to Acute Lung Injury

“…Neutrophils are a major source of lactoferrin. Normal lactoferrin levels in the blood are very low with 1 μg/mL, but under septic conditions these can rise up to 200 μg/mL and are likely to be higher at the inflammatory site itself (160). Besides its antimicrobial activity, lactoferrin exhibits immune-modulating activities.…”

Porcine lactoferrin as feedstuff additive elevates avian immunity and potentiates vaccination

“…LF stimulates the differentiation of T cells from immature precursors (Li et al 2006). Studies performed under nonpathogenic conditions have indicated that LF supports the proliferation and differentiation of Th cells into Th1 or Th2 cell types.…”