Rapid adhesive responses of endothelial cells and of neutrophils induced by leukotriene B4 are mediated by leucocytic adhesion protein CD18.
Controversy has existed as to the ability of leukotriene B4 (LTB4) to enhance adhesive properties of human neutrophils (PMN) and endothelial cells. We found that LTB4 induced a rapid but transient adhesion of PMN to an albumin-coated plastic surface and to cultured human umbilical vein endothelial cells (HUVEC). Although the adhesive response of PMN to the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) was longer lasting, peak hyperadherence was of similar magnitude as to LTB4 and was less susceptible to assay conditions. Adherence induced by either LTB4 or fMLP could be abrogated by the monoclonal antibody 60.3, indicating similar dependence on the leucocyte adhesion protein CD18. Lipoxin A did not induce PMN hyperadherence. Treating HUVEC with LTB4, but not with its omega-oxidized metabolites 20-OH- and 20-COOH-LTB4, lipoxin A, or with fMLP conferred a rapid, dose-related, enhanced adhesion of PMN. This effect was dependent on CD18 and on divalent cations. It disappeared with prolonged exposure to LTB4, required a metabolically active HUVEC, and was not due to passive binding of LTB4 to HUVEC. Thus, LTB4 induces a transient expression of hyperadhesiveness in HUVEC as well as in neutrophils, and both effects are dependent on expression of CD18.
Lindström
P
P
Department of Medicine III, Karolinska Institute, Södersjukhuset, Stockholm, Sweden.
Lerner
R
R
Palmblad
J
J
Patarroyo
M
M
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4 / Q000502:physiology*; D044045:Lipoxins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000166:cytology*; D010969:Plastics; D010972:Platelet Activating Factor; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology*; D013917:Thrombin
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; D010969:Plastics; D010972:Platelet Activating Factor; D016028:Receptors, Leukocyte-Adhesion; C040527:lipoxin A4; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013917:Thrombin