Tsugio Nakazawa

Toll-like receptor 4 surface expression on human monocytes and B cells is modulated by IL-2 and IL-4

Human Toll-like receptor 4 (TLR4) has recently been identified, and it has been shown to be the main protein involved in recognizing gram-negative bacteria. We examined the regulation of TLR4 surface expression in human peripheral blood monocytes and B cells by interleukin-2 (IL-2) and IL-4. IL-2 up-regulated TLR4 surface expression on human peripheral blood monocytes, but did not change expression on human peripheral B cells. By contrast, IL-4 down-regulated TLR4 surface expression on human peripheral blood monocytes, but up-regulated TLR4 surface expression on human peripheral B cells. These results indicate that Th1 cytokine IL-2 enhances receptors involved in the response to gram-negative bacteria and that activation of cellular immunity may enhance defense against these pathogens through monocytes, but not B cells, whereas Th2 cytokine IL-4 modulates the receptor response to gram-negative bacteria and that activation of humoral immunity may enhance defense against these pathogens through B cells, but not monocytes.

Toll-like receptor 2 and 4 surface expressions on human monocytes are modulated by interferon-γ and macrophage colony-stimulating factor

Abstract Human Toll-like receptor 2 (TLR2) and TLR4 are recently identified receptors. TLR4 was shown to be the main protein involved in recognizing Gram-negative bacteria, whereas TLR2 is apparently the key factor in responses to other types of microbial pathogens. We examined regulations of TLR2 and TLR4 surface expressions in human peripheral blood monocytes by interferon-γ (IFN-γ) and macrophage colony-stimulating factor (M-CSF). IFN-γ up-regulated both TLR2 and TLR4, but enhanced the surface expression, on human peripheral blood monocytes of TLR4 more than that of TLR2. On the other hand, M-CSF up-regulated both TLR2 and TLR4 surface expression on human peripheral blood monocytes, with no change in the ratio of TLR2/TLR4 surface expression. These results indicate that IFN-γ enhances receptors involved in the response to Gram-negative bacteria more than those involved in responses to other types of microbial pathogens, whereas M-CSF enhances the receptor response to Gram-negative bacteria in the same manner as to other types of microbial pathogens.

Induction of Toll-like receptor 4 in granulocytic and monocytic cells differentiated from HL-60 cells

Toll‐like receptor 4 (TLR4) is the main protein expressed on the cell surface and is an essential receptor for lipopolysaccharide (LPS) signalling in human peripheral blood leucocytes. We examined TLR4 expression and the functional response to LPS in retinoic acid‐treated HL‐60 cells (HL‐60‐derived granulocytic cells) and interferon‐γ‐treated HL‐60 cells (HL‐60‐derived monocytic cells). Slight TLR4 expression was induced in HL‐60‐derived granulocytic cells, while strong induction was seen in HL‐60‐derived monocytic cells. LPS induced interleukin 1β (IL‐1β) production and TLR4 expression in HL‐60‐derived monocytic cells, but not HL‐60‐derived granulocytic cells. These data indicate different responses to LPS in the cells. TLR4 surface expression paralleled LPS‐induced phagocytosis and TLR4‐neutralizing antibody partially inhibited LPS‐induced IL‐8 production in HL‐60‐derived monocytic cells, but not in HL‐60‐derived granulocytic cells. These results suggest that HL‐60‐derived monocytic cells are partially activated via TLR4, but that HL‐60‐derived granulocytic cells are not activated via TLR4.

Yearly and Seasonal Changes of Specific IgE to Japanese Cedar Pollen in a Young Population

BACKGROUND There have been no detailed long-term observations of the relationship between specific IgE production and stimulation by various naturally occurring allergens. OBJECTIVE This study was conducted to elucidate the yearly and seasonal changes of specific IgE antibody production to Japanese cedar pollen, an allergen of Japanese cedar pollinosis, in young adults. METHODS The number of Japanese cedar pollen were counted over a period of 9 years. Changes in the percentages of antibody carriers to Japanese cedar pollen and mite were examined during these years. Changes in Japanese cedar pollen-specific IgE levels between a low exposure year and a high exposure year in individual subjects were also investigated. RESULTS From 1987 to 1995, the percentages of Japanese cedar pollen-IgE carriers varied from about 30% to 50% with the intensity of pollen stimulation, and carriers tended to increase yearly. The rates of anti-mite IgE carriers changed little. In the spring which is the pollen season, Japanese cedar pollen-IgE levels in low exposure years were weaker than those in high exposure years in individual subjects. Levels in autumn, which is not the pollen season, showed equivalent levels in both high and low exposure years. Anti-mite IgE levels in individual subjects varied little during these years. CONCLUSIONS A long-term follow-up study supported that Japanese cedar pollen-IgE production is mainly associated with the degree of allergen exposure.

Mechanical fluid flow and surfactant-ta influence activation of macrophages

SummaryWe examined the effect of mechanical fluid flow and surfactant on macrophage aggregation as the indication of macrophage activation. Mechanical fluid flow enhanced aggregation in phorbol myristate acetate (PMA)-treated human myeloid leukemic cell lines (HL-60 cells), but had no effect on differentiation of PMA-treated HL-60 cells. Surfactant-TA (an artificial surfactant) inhibited fluid flow-induced aggregation, but had no effect on differentiation of PMA-treated HL-60 cells. Human alveolar macrophages spontaneously formed small aggregates without stimulation. This aggregation was enhanced by fluid flow and inhibited by surfactant-TA. Taken together, these data suggest that macrophage activation is affected by fluid flow and surfactants.