TY - JOUR
T1 - Absence of PI3Kγ leads to increased leukocyte apoptosis and diminished severity of experimental autoimmune encephalomyelitis
AU - Rodrigues, David Henrique
AU - Vilela, Márcia de Carvalho
AU - Barcelos, Lucíola da Silva
AU - Pinho, Vanessa
AU - Teixeira, Mauro Martins
AU - Teixeira, Antônio Lúcio
PY - 2010/5
Y1 - 2010/5
N2 - Phosphatidylinositol-3-kinase γ (PI3Kγ) plays an important role in the motility of leukocytes in several models of inflammation. In this work, the role of PI3Kγ in experimental autoimmune encephalomyelitis (EAE) was investigated. EAE was induced in wild-type and PI3Kγ deficient mice (PI3Kγ-/-). WT animals had a peak of clinical symptoms around day 14 post-induction (p.i.). PI3Kγ-/- animals developed milder EAE signs and peak of disease was noticed only on day 21 p.i. Better clinical outcome correlated with the absence of perivascular cuffs on day 14 p.i. and with decreased levels of CCL2 and CCL5 in brain of PI3Kγ-/- mice. There was increased leukocyte rolling and adhesion in pial vessels, as assessed by intravital microscopy, at day 14 after EAE induction in WT mice. The latter parameters were unaltered in PI3KThere was increased le-/- mice subjected to EAE. Moreover, the PI3KThere was increased le inhibitor AS-605240 given just before the intravital microscopy failed to affect leukocyte rolling or adhesion. Finally, there was a significant increase in the number of apoptotic cells in the CNS of EAE-induced PI3KThere was increased le-/- mice. Our results suggest that PI3KThere was increased le is involved in EAE and plays a more important role in mediating leukocyte survival than leukocyte adhesion in this experimental model of multiple sclerosis.
AB - Phosphatidylinositol-3-kinase γ (PI3Kγ) plays an important role in the motility of leukocytes in several models of inflammation. In this work, the role of PI3Kγ in experimental autoimmune encephalomyelitis (EAE) was investigated. EAE was induced in wild-type and PI3Kγ deficient mice (PI3Kγ-/-). WT animals had a peak of clinical symptoms around day 14 post-induction (p.i.). PI3Kγ-/- animals developed milder EAE signs and peak of disease was noticed only on day 21 p.i. Better clinical outcome correlated with the absence of perivascular cuffs on day 14 p.i. and with decreased levels of CCL2 and CCL5 in brain of PI3Kγ-/- mice. There was increased leukocyte rolling and adhesion in pial vessels, as assessed by intravital microscopy, at day 14 after EAE induction in WT mice. The latter parameters were unaltered in PI3KThere was increased le-/- mice subjected to EAE. Moreover, the PI3KThere was increased le inhibitor AS-605240 given just before the intravital microscopy failed to affect leukocyte rolling or adhesion. Finally, there was a significant increase in the number of apoptotic cells in the CNS of EAE-induced PI3KThere was increased le-/- mice. Our results suggest that PI3KThere was increased le is involved in EAE and plays a more important role in mediating leukocyte survival than leukocyte adhesion in this experimental model of multiple sclerosis.
KW - Chemokines
KW - Experimental autoimmune encephalomyelitis
KW - Intravital microscopy
KW - Phosphatidylinositol-3-kinase There was increased le
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U2 - 10.1016/j.jneuroim.2010.02.016
DO - 10.1016/j.jneuroim.2010.02.016
M3 - Article
C2 - 20303183
AN - SCOPUS:77952279397
SN - 0165-5728
VL - 222
SP - 90
EP - 94
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -