FMLP actions and its binding sites in isolated human coronary arteries

Mitsumasa Keitoku, Masahiro Kohzuki, Hiroshi Katoh, Masayuki Funakoshi, Shu Suzuki, Masaharu Takeuchi, Akihiko Karibe, Satoru Horiguchi, Jun Watanabe, Shoichi Satoh, Masato Nose, Keishi Abe, Hiroshi Okayama, Kunio Shirato

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

The chemoattractant f-Met-Leu-Phe (FMLP) can modulate human coronary arterial tone without the involvement of peripheral leukocytes. We investigated the actions of FMLP and its cellular mechanism in human coronary arteries isolated 2-3 h after death. A single dose of FMLP (0.01-10 μM) produced transient contraction (or, followed by relaxation) responses in most human coronary rings examined. These responses to FMLP were in large part mediated by the generation of cyclooxygenase products, mainly thromboxane A2 (TXA2) and prostaglandin I2 (PGI2). Radiolabeled N-formyl hexapeptide, 125I-f-Nle-Leu-Phe-Nle-Tyr-Lys bound densely to intimal and adventitial sites that accumulated macrophages (CD68-positive) with a K(d) of 14-29 nM and, further, weakly to the media with a K(d) of 2.4-3.6 μM. Several cell types including macrophages, endothelial cells and smooth muscle cells were positively immunostained for both TXA2 synthase and PGI2 synthase. However, there was no significant relation between the magnitude of the responses to FMLP and dense macrophage accumulation in the intimal plaques or the adventitia. A reverse transcription-polymerase chain reaction showed predominant expression of FMLP receptor homologues, FPRH1 and FPRH2 mRNA, in human coronary medial tissues relative to that in leukocytes. In conclusion, FMLP produced transient tension changes in human coronary arteries, mainly via the generation of TXA2 and PGI2. This effect of FMLP did not appear to be mediated by the activation of densely accumulated intimal and/or adventitial macrophages, but by the activation of unidentified medial tissue cells which might have functional FMLP receptor homologues.

Original languageEnglish
Pages (from-to)881-894
Number of pages14
JournalJournal of Molecular and Cellular Cardiology
Volume29
Issue number3
DOIs
Publication statusPublished - 1997 Mar

Keywords

  • Atherosclerosis
  • Chemoattractants
  • Coronary vasospasm
  • Macrophages
  • Prostaglandin
  • Thromboxane

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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