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CD40‐dependent inflammatory and thrombogenic responses to soluble CD40 ligand in the microvasculature
Author(s) -
Stokes Karen Yvonne,
Gurwara Shelly,
Granger D. Neil
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a704-b
Subject(s) - cd40 , platelet , inflammation , in vivo , intravital microscopy , platelet activation , chemistry , endothelium , vasodilation , immunology , medicine , pharmacology , microcirculation , in vitro , biology , biochemistry , cytotoxic t cell , microbiology and biotechnology
Levels of the soluble form of CD40L (sCD40L) are elevated in patients with several inflammatory conditions including hypercholesterolemia and following stroke. However it remains unclear whether sCD40L can initiate inflammatory alterations in vivo, or is merely a marker of inflammation. The objectives of this study were to determine whether sCD40L promotes inflammatory and thrombogenic responses in the microvasculature and whether these events are mediated through CD40. Intravital videomicroscopy was used to quantify arteriolar responses to acetylcholine, and leukocyte and platelet adhesion in venules of wildtype, and CD40 knockout (ko) mice receiving vehicle or recombinant sCD40L (1 μg or 10 ng) i.v. prior to observation. Initial findings revealed that 1 μg sCD40L initiated leukocyte recruitment within 2 h, peaking at 5–6 h post‐administration. Focusing on 5.5 h post‐sCD40L, platelet adhesion was also increased and arteriolar vasodilation to acetylcholine was impaired in wildtype mice by both doses of sCD40L (vs vehicle). However, sCD40L failed to induce leukocyte and platelet adhesion in CD40ko mice, and arteriolar function was comparable to control levels. Our findings indicate that sCD40L may promote inflammatory and thrombogenic responses in vivo through interaction with CD40. This may have important implications in patients with elevated levels of sCD40L. (Supported by HL26441).