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Transendothelial pressure inhibits neutrophil migration across IL‐1‐treated endothelial cells: a role for nitric oxide.
Author(s) -
Zheng Zhilan,
Rumbaut Rolando E,
Burns Alan R
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.20.5.a1159-d
Subject(s) - nitric oxide , umbilical vein , endothelium , chemistry , endothelial stem cell , hydrostatic pressure , nitric oxide synthase , monolayer , adhesion , human umbilical vein endothelial cell , biophysics , microbiology and biotechnology , in vitro , biochemistry , biology , endocrinology , organic chemistry , physics , thermodynamics
Hydraulic conductivity ( L p) across an endothelial monolayer increases in response to transendothelial pressure. Increased transendothelial pressure (and L p) occurs in a variety of pathophysiological conditions and this increase is presumably mediated by a nitric oxide‐cAMP‐dependent mechanism (Tarbell et al. , J. Appl. Physiol. 87:261, 1999). We sought to determine whether increased transendothelial pressure regulates neutrophil transmigration. IL‐1‐treated human umbilical vein endothelial cell monolayers were cultured on a polycarbonate membrane filter and placed in a custom fluid‐filled chamber with or without a transendothelial pressure gradient (10cm H 2 O). Freshly isolated neutrophils were added and allowed to settle and interact with the monolayer for 15 minutes. In some cases, the monolayers were pre‐treated with the nitric oxide synthase inhibitor L‐NAME (or its control, D‐NAME). Transendothelial pressure significantly reduced neutrophil migration from 40% down to 5% ( p ≤0.05). This reduction in migration was completely prevented by L‐NAME, but not D‐NAME. In the presence of a transendothelial pressure gradient, endothelial nitric oxide detection increased 1.8‐fold ( p ≤0.05) using a fluorescence‐based assay (DAF‐2DA). In the absence of transendothelial pressure, addition of a nitric oxide donor (deta NO, 2.5μM) reduced neutrophil migration (but not adhesion) across IL‐1‐treated HUVEC monolayers by 50%. Collectively, these studies show that transendothelial pressure inhibits neutrophil transmigration through a nitric oxide‐dependent mechanism. Supported by NIH HL‐64721, AI‐46773, HL‐70537, and HL‐42550.