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Soluble CD40 ligand stimulates functional microparticle release from pulmonary microvascular endothelium
Author(s) -
Rai Jyoti,
King Judy A,
Moore Tim M,
Bauer Natalie N
Publication year - 2009
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.23.1_supplement.771.8
Subject(s) - alcam , ve cadherin , chemistry , endothelium , microbiology and biotechnology , barrier function , microparticle , inflammation , immunology , endothelial stem cell , cell , biophysics , in vitro , medicine , biology , biochemistry , astrobiology
Plasma sCD40L levels are elevated during diseases involving activation of immune, inflammatory, and coagulation cascades. During inflammatory states microparticles, small vesicular segments of cell membrane, increase yet it remains unknown whether the pulmonary vascular bed contributes to the increase in number and what the function of these microparticles may be. Our hypothesis is that sCD40L stimulates an increase in endothelial microparticle (EMP) release from the pulmonary microvasculature which function as regulators of vascular repair. Treatment of PMVECs with sCD40L (1 µg/mL, 1 hour) stimulated a two‐fold increase in EMP number as compared to basal EMP production. This increase was inhibited by pre‐treatment of PMVECs with anti‐CD40 antibody (0.5ug/ml, 1 hr.). When PMVEC monolayers were disrupted with trypsin, treatment of these monolayers with sCD40L‐EMPs significantly reduced barrier resealing. It has previously been reported that PMVECs express activated leukocyte cell adhesion molecule (ALCAM) and suggested that ALCAM plays a role in barrier integrity. To determine whether ALCAM was expressed in EMPs we examined them by TEM. We determined that sCD40L‐EMPs carry ALCAM which may provide a mechanism by which binding of EMPs to disrupted cells could inhibit proper barrier resealing. Support: Parker B. Francis Fellowship (Bauer and Moore), AHA #0765413B (N. Bauer) and 0765421B (T. Moore).