TY - JOUR
T1 - IL-3 is required for increases in blood basophils in nematode infection in mice and can enhance IgE-dependent IL-4 production by basophils in vitro
AU - Lantz, Chris S.
AU - Min, Booki
AU - Tsai, Mindy
AU - Chatterjea, Devavani
AU - Dranoff, Glenn
AU - Galli, Stephen J.
N1 - Funding Information:
We thank Fred Finkelman and William Paul and their colleagues for helpful comments. Supported by NIH Grants AI23990, CA72074 and HL67674 to SJG, NIH Grant AI049932 and Jeffress Memorial Trust Grant J-782 to CSL, and startup funds from the Cleveland Clinic Foundation to BM; BM is the recipient of the career development grant from the American Heart Association.
PY - 2008/11
Y1 - 2008/11
N2 - Basophils represent potential effector and immunoregulatory cells, as well as a potential source of IL-4, during the immune response elicited by infection with the nematode Nippostrongylus brasiliensis (N.b.), and in other settings. However, the factors which regulate the numbers of blood basophils in mice, or the ability of these cells to produce IL-4, are not fully understood. We found that infection of mice with the nematodes N.b. or Strongyloides venezuelensis (S.v.) induced substantial increases in the numbers of blood basophils (to as high as 18% of circulating blood leukocytes). Experiments in IL-3-/- vs IL-3+/+ mice, and in IL-3-treated IL-3-/- mice, showed that essentially all of the increases in blood or bone marrow basophils during N.b. or S.v. infection were IL-3 dependent. Many of the blood, bone marrow or liver-derived basophils from IL-3-/- or IL-3+/+ mice expressed intracellular IL-4 upon stimulation with anti-IgE in vitro. However, after incubation of the cells with exogenous IgE in vitro, blood- or liver-derived basophils from IL-3+/+ mice exhibited higher levels of intracellular IL-4 after stimulation with anti-IgE than did basophils derived from IL-3-/- mice. Thus, IL-3 is a major regulator of the marked increases in blood basophil levels observed during infection of mice with N.b. or S.v. and also can enhance levels of intracellular IL-4 upon activation of basophils with anti-IgE in vitro.
AB - Basophils represent potential effector and immunoregulatory cells, as well as a potential source of IL-4, during the immune response elicited by infection with the nematode Nippostrongylus brasiliensis (N.b.), and in other settings. However, the factors which regulate the numbers of blood basophils in mice, or the ability of these cells to produce IL-4, are not fully understood. We found that infection of mice with the nematodes N.b. or Strongyloides venezuelensis (S.v.) induced substantial increases in the numbers of blood basophils (to as high as 18% of circulating blood leukocytes). Experiments in IL-3-/- vs IL-3+/+ mice, and in IL-3-treated IL-3-/- mice, showed that essentially all of the increases in blood or bone marrow basophils during N.b. or S.v. infection were IL-3 dependent. Many of the blood, bone marrow or liver-derived basophils from IL-3-/- or IL-3+/+ mice expressed intracellular IL-4 upon stimulation with anti-IgE in vitro. However, after incubation of the cells with exogenous IgE in vitro, blood- or liver-derived basophils from IL-3+/+ mice exhibited higher levels of intracellular IL-4 after stimulation with anti-IgE than did basophils derived from IL-3-/- mice. Thus, IL-3 is a major regulator of the marked increases in blood basophil levels observed during infection of mice with N.b. or S.v. and also can enhance levels of intracellular IL-4 upon activation of basophils with anti-IgE in vitro.
KW - Allergy
KW - Cytokines
KW - Immune response
KW - Inflammation
KW - Mast cells
KW - Parasites
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U2 - 10.1038/labinvest.2008.88
DO - 10.1038/labinvest.2008.88
M3 - Article
C2 - 18975389
AN - SCOPUS:54949113206
SN - 0023-6837
VL - 88
SP - 1134
EP - 1142
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 11
ER -