Leukotriene B4 enhances IL-4-induced IgE production from normal human lymphocytes.
Interleukin 4 (IL-4)-induced IgE production by normal peripheral blood mononuclear cells (PBMC) and E- cells (PBMC partially depleted of T cells) was significantly enhanced by leukotriene B4(LTB4) in a dose-dependent manner, whereas LTB4 by itself was not effective for IgE production. The potentiating effect of LTB4 was strictly dependent on IL-4. When PBMC or E- cells were primed with IL-4 (300 U/ml) for 48 hr, then recultured with LTB4 alone (10(-10) to 10(-8) M), increased IgE production was observed. Maximum enhancement of IgE production after IL-4 priming was achieved using a combination of IL-4 and LTB4, acting additively. Moreover, the potentiating effect of LTB4 on IL-4-induced IgE production was completely dependent on the presence of a monocyte/macrophage population. This effect of LTB4 was completely abolished by depletion of monocytes and recovered by reconstitution with autologous monocytes. From the study of IL-4 receptor (IL-4R) expression determined by flow cytometry, IL-4 was found to upregulate the biotinylated-IL-4 (B-IL-4)/streptavidin binding to both T- and B-cell populations. A further increase of B-IL-4 binding was obtained when the cells were incubated with IL-4 and LTB4. Finally, LTB4 can induce soluble CD23 (sCD23) release by E- cells tested either alone or in the presence of IL-4. Taken together, these data suggest that LTB4 can influence the IL-4-induced IgE production through, at least, a bimodal action, i.e., increase of IL-4R positive cells and release of sCD23. These findings may be a specific feature of LTB4 which provides a crucial role in IL-4-linked allergic inflammatory process.
Yamaoka
K A
KA
U365-Institut National de la Santé et de la Recherche Médicale (INSERM), Interferons et Cytokines, Institut Curie, Paris, France.
Dugas
B
B
Paul-Eugene
N
N
Mencia-Huerta
J M
JM
Braquet
P
P
Kolb
J P
JP
D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000494:pharmacology*; D008214:Lymphocytes / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D017455:Receptors, IgE / Q000737:chemistry / Q000378:metabolism; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000378:metabolism; D012995:Solubility
D017455:Receptors, IgE; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D007975:Leukotriene B4; D015847:Interleukin-4; D007073:Immunoglobulin E