Chemotaxins inhibit neutrophil adherence to and transmigration across cytokine-activated endothelium: correlation to the expression of L-selectin.
Non-activated neutrophils strongly adhere to cytokine-activated human umbilical vein endothelial cells (HUVE). However, activation of neutrophils by different chemotactic mediators led to potent inhibition of this endothelial-dependent interaction. For different formylated peptides, concentrations leading to maximal adherence inhibition coincided with those known for inducing maximal chemotactic migration of neutrophils. In terms of maximal adherence inhibition, a rank list was found in the order of N-formyl-Met-Leu-Phe > C5adesArg > interleukin-8 > C5a > or = leukotriene B4, whereas platelet-activating factor, and lipopolysaccharide showed no inhibition. This rank order was congruent to that of down-regulation of neutrophil L-selectin detected by the monoclonal antibody Leu-8. Moreover, the dose-dependent increase of neutrophil adherence inhibition corresponded to the loss of L-selectin expression. Concentrations higher than that required for maximal inhibition led to a dose-dependent decrease of inhibition, which was accompanied by increasing expression of neutrophil CD11/CD18. In contrast to the capacity of non-activated neutrophils to migrate across interleukin-1-activated HUVE monolayers, transmigration was significantly impaired after chemotactic activation.
Moser
R
R
Department of Medicine, University Hospital, Zürich, Switzerland.
Olgiati
L
L
Patarroyo
M
M
Fehr
J
J
D015703:Antigens, CD / Q000378:metabolism; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D019041:L-Selectin; D008070:Lipopolysaccharides / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine