Stimulation of neutrophil adherence to vascular endothelial cells by histamine and thrombin and its inhibition by PAF antagonists and dexamethasone

M. Watanabe, M. Yagi, M. Omata, N. Hirasawa, S. Mue, S. Tsurufuji, K. Ohuchi

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

1 In order to clarify the roles of platelet-activating factor (PAF) in histamine- and thrombin-induced neutrophil adhesion to vascular endothelial cells, the effects of several PAF antagonists were examined. The effects of the glucocorticoid dexamethasone were also examined in order to gain further insight into the anti-inflammatory actions of glucocorticoids. 2 In culture, histamine and thrombin stimulated the adherence of rat peritoneal neutrophils to human endothelial cells from the umbilical vein. They did not stimulate neutrophil adherence in the absence of endothelial cells, suggesting that the target cells for the histamine; and thrombin-induced adherence of neutrophils were endothelial cells, not neutrophils. 3 Several PAF antagonist, such as CV-3988, L-652,731 and Y-24,180 inhibited the histamine- and thrombin-induced neutrophil adherence in a concentration-dependent manner. Indomethacin failed to inhibit it. 4 Dexamethasone, a steroidal anti-inflammatory drug, did not inhibit the histamine- and thrombin-induced adherence of neutrophils to endothelial cells when the drug was present only during the 20 min incubation period for the adherence assay. When the endothelial cells were preincubated for 3 h with dexamethasone, the adherence of neutrophils to endothelial cells induced by histamine or thrombin was not inhibited. 5 When the neutrophils were preincubated for 3 h with dexamthasone, the histamine- and thrombin-induced adherence of neutrophils to endothelial cells was inhibited. 6 Our studies indicate that: (a) adherence of neutrophils to endothelial cells induced by histamine and thrombin is mediated by PAF production since PAF antagonists inhibited the adherence of neutrophils; and (b) neutrophils, not endothelial cells, are the target cells through which dexamethasone acts to inhibit adherence.

Original languageEnglish
Pages (from-to)239-245
Number of pages7
JournalBritish Journal of Pharmacology
Volume102
Issue number1
DOIs
Publication statusPublished - 1991

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Stimulation of neutrophil adherence to vascular endothelial cells by histamine and thrombin and its inhibition by PAF antagonists and dexamethasone'. Together they form a unique fingerprint.

Cite this