Signal transduction mechanisms for leukotriene B4 induced hyperadhesiveness of endothelial cells for neutrophils.
We have previously demonstrated that leukotriene B4 (LTB4) induces in vitro a transient state of hyperadhesiveness in cultured human umbilical vein endothelial cells (HUVEC) for neutrophils (PMN). The magnitude of this response is intermediate of that conferred by thrombin and by platelet-activating factor (PAF). This report shows that the LTB4 response was neither related to HUVEC expression of PAF (because it could not be blocked by the PAF receptor antagonist WEB-2086), nor to access to LTB4 receptors on neutrophils (as shown by LTB4 receptor desensitization experiments). However, it could be partly blocked by treating HUVEC with an LTB4 receptor antagonist (SC-41930). LTB4 evoked a rise of intracellular calcium concentrations, [Ca2+]i, in the HUVEC, and the hyperadhesive HUVEC response to LTB4 was abrogated by buffering of [Ca2+]i by Quin-2. The response was not inhibited by treating HUVEC with pertussis toxin before LTB4. Neutrophils showed no signs of activation when adhering to LTB4-treated HUVEC because they did not i) release lactoferrin, or ii) react with an increase of [Ca2+]i, and iii) they bound equally well to the stimulated endothelial cells after having been treated with pertussis toxin so that up-regulation of PMN adhesion to LTB4 was abolished. LTB4-treated HUVEC did not shed factors that modulated neutrophil adherence or chemotaxis. Thus, LTB4 promotes HUVEC hyperadhesiveness for PMN, and the transduction mechanism involves calcium ions, may depend on a surface receptor for LTB4, but does not involve pertussis toxin-sensitive G proteins or PMN activation.
Palmblad
J
J
Department of Medicine, Karolinska Institute, Stockholm Söder Hospital, Sweden.
Lerner
R
R
Larsson
S H
SH
D002413:Cations, Divalent / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D007975:Leukotriene B4 / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000502:physiology; D018102:Receptors, Leukotriene B4 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D002413:Cations, Divalent; D010972:Platelet Activating Factor; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4; D019204:GTP-Binding Proteins