Regular Contributions
Stimulated Neutrophils Evoke Signal
Transduction to Increase Vascular Permeability in Rat Lungs
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TATSUO TANITA,
CHUN SONG, HIROSHI
KUBO, SADAFUMI ONO,
MOTOYASU SAGAWA,
MASAMI SATO, YUJI
MATSUMURA, TAKASHI
KONDO and SHIGEFUMI
FUJIMURA 1 and YASUTO
ITOYAMA
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Department of Thoracic Surgery,
Institute of Development, Aging and Cancer, Tohoku University,
Sendai 980-8575
The mechanisms by which
stimulated neutrophils (PMNs) damage pulmonary vascular endothelium
were investigated using twenty-four perfused lung preparations
isolated from rats. We tested the ability of unstimulated and
mechanically stimulated PMNs to adhere to pulmonary endothelial cells
and, thereby, alter pulmonary vascular permeability (measured as the
pulmonary filtration coefficient) and hemodynamics. To stimulate
PMNs, they were gently agitated in a glass vial for 10 seconds.
Perfusing lungs with the stimulated PMNs (stimulated group) elicited
a 3-fold increase in the filtration coefficient as compared to lungs
perfused with unstimulated cells (unstimulated group). This increase
in filtration was completely blocked by preincubation of stimulated
PMNs with CD18 monoclonal antibody (MoAb group). This increase in
filtration coefficient was also completely blocked by GF109203X, a
protein kinase C inhibitor (GF group). Pulmonary vascular resistance
increased when the stimulated PMNs were injected to the isolated
lungs. Although, preincubation of stimulated PMNs with CD18 MoAb
successfully blocked and GF109203X partly blocked this increase in
pulmonary vascular resistance. The accumulation of stimulated PMNs
within the lungs, as assessed by myeloperoxidase (MPO) levels, was
blocked by preincubation of stimulated PMNs with CD18 MoAb. However,
GF109203X did not decrease MPO levels. These findings suggest that
stimulated PMN-induced increases in pulmonary vascular filtration,
resulted from endothelial cell injury caused by adhesion to the
endothelial cells, evoke intracellular signaling within the
endothelial cells.
Key words--- adhesion molecules; GF109203X;
neutrophils; protein kinase C; pulmonary vascular
filtration
© 1999 Tohoku University Medical Press
Tohoku J. Exp. Med., 1999,
189, 213-225
Address for reprints: Tatsuo Tanita, Department of Thoracic
Surgery, Institute of Development, Aging and Cancer, Tohoku
University, 4-1 Seiryomachi, Aoba-ku, Sendai 980-8575, Japan.
e-mail: tanita@idac.tohoku.ac.jp
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