Role of nitric oxide in human pulmonary microvascular endothelial cell adhesion

Hirokazu Tsukahara, Eisei Noiri, Mi Zu Jiang, Masahiro Hiraoka, Mitsufumi Mayumi

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


We examined the effect of nitric oxide (NO) on cell adhesion using cultured human pulmonary microvascular endothelial cells (PMVEC). Attachment of these cells to fibronectin was significantly inhibited by NO donors, spermine NONOate and S-nitroso-N-acetyl-penicillamine or L-arginine, but not 8-bromoguanosine-3',5'-cyclic-monophosphate. Similar results were obtained with the electrical cell-substrate impedance sensor (ECIS) technique. Addition of NO donors or L-arginine, but not 8-bromoguanosine-3',5'-cyclic- monophosphate or N2,2'-O-dibutyrylguanosine-3',5'-cyclic-monophosphate, to confluent PMVEC monolayers resulted in a transient decrease in cell adhesion, which was quantitated by the ECIS. Exposure to 1 U/ml α-thrombin reduced the monolayer electrical resistance by ~50%. The observed response was significantly suppressed by pretreatment of cells with intracellular calcium chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid or NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester, but not guanylate cyclase inhibitor, 6-anilino-5,8-quinoline-quinone. Selective knockout of endothelial NO synthase with antisense oligodeoxynucleotides also significantly reduced thrombin-induced decrease in monolayer resistance. Our findings indicate that thrombin stimulates calcium-dependent release of NO from PMVEC, which mediates the retraction of endothelial cells via a cGMP- independent pathway. Our results suggest that NO modulates cell-matrix and/or cell-cell adhesion in PMVEC and that this molecule might modify microvascular permeability in the human lung. (C) 2000 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalLife Sciences
Issue number1
Publication statusPublished - May 26 2000
Externally publishedYes


  • Cell adhesion
  • Electrical cell-substrate impedance sensor
  • Human
  • Nitric oxide
  • Pulmonary microvascular endothelial cell

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)


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