In vitro inhibitory effect of IL-8 and other chemoattractants on neutrophil-endothelial adhesive interactions.
We have previously reported that cytokine- or LPS-activated human umbilical vein endothelial cell (HUVEC) monolayers secrete IL-8 that can act as a neutrophil-selective adhesion inhibitor. In our study we investigated the mechanisms involved in the leukocyte adhesion inhibitory action of IL-8. The leukocyte adhesion inhibitory effect appears to be mediated by the action of IL-8 on the neutrophil, does not involve down-regulation of relevant endothelial adhesion molecules such as endothelial-leukocyte adhesion molecule-1 or intercellular adhesion molecule-1, and is quantitatively similar in different endothelial activation states that are predominantly endothelial-leukocyte adhesion molecule-1 dependent or intercellular adhesion molecule-1 dependent. In addition to inhibiting the attachment of freshly isolated peripheral blood neutrophils to cytokine-activated HUVEC monolayers, IL-8 also promoted a rapid detachment of tightly adherent neutrophils from activated HUVEC, and abolished neutrophil transendothelial migration. Certain other chemoattractants, including FMLP and C5a, had similar inhibitory actions, indicating IL-8 was not unique in its ability to inhibit various neutrophil-endothelial interactions. In contrast, two other neutrophil agonists 1-0-alkyl-2-acetyl sn-glycero-3-phosphocholine and granulocyte-macrophage-CSF, which, like IL-8, are produced by activated HUVEC, as well as the leukocyte-derived chemoattractant leukotriene B4, exerted minimal inhibitory effects on adhesion. Regardless of their ability to modulate neutrophil-endothelial cell adhesion, all these agents induced altered leukocyte surface expression of functionally important adhesion molecules, including loss of L-selectin (leukocyte adhesion molecule-1, LECAM-1) and increase in CD11b/CD18. Thus, although the above agonists have been characterized primarily as chemoattractants, our findings demonstrate that these agents can exert a wide range of modulatory effects on neutrophil-endothelial adhesive interactions.
Luscinskas
F W
FW
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115.
Kiely
J M
JM
Ding
H
H
Obin
M S
MS
Hébert
C A
CA
Baker
J B
JB
Gimbrone
M A
MA
D015703:Antigens, CD / Q000378:metabolism; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology*; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D016209:Interleukin-8 / Q000494:pharmacology*; D019041:L-Selectin; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology*
D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; D016207:Cytokines; D019040:E-Selectin; D006680:HLA Antigens; D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin