Stimulated neutrophils evoke signal transduction to increase vascular permeability in rat lungs

Tatsuo Tanita, Chun Song, Hiroshi Kubo, Sadafuhi Ono, Motoyasu Sagawa, Masami Sato, Yuji Matsumura, Takashi Kondo, Shigefumi Fujimura

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)213-225
Number of pages13
JournalTohoku Journal of Experimental Medicine
Volume189
Issue number3
DOIs
Publication statusPublished - 1999 Nov

Keywords

  • Adhesion molecules
  • GF109203X
  • Neutrophils
  • Protein kinase C
  • Pulmonary vascular filtration

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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