Leukocyte inhibitory factor stimulates neutrophil-endothelial cell adhesion.
We investigated the ability of the human lymphokine leukocyte inhibitory factor (LIF) to modulate neutrophil-endothelial cell (EC) adherence. EC were cultured from collagenase-treated human umbilical cord veins and grown in complete medium supplemented with EC growth factor. Adherence was measured as the percent of 51Cr-labeled neutrophils remaining adherent to the EC after gentle lavage. Polymorphonuclear neutrophils (PMN) were pretreated with LIF (0.5 to 8 U/ml), extensively washed, and allowed to interact with the EC monolayers. LIF was demonstrated to induce an increase in the capacity of PMN to bind EC in a dose-dependent fashion (from 30.9 +/- 2.1% adherence with control-treated PMN to 68.6 +/- 3.0% at 4 U LIF; p less than 0.001). In subsequent experiments we demonstrated that 10 min was a sufficient preincubation time for LIF to modulate the capacity of the PMN to adhere to EC. LIF has previously been observed to up-regulate expression of C receptor type 3 on PMN, a receptor which has been shown to be involved in PMN-EC binding. Exposure of PMN to anti-C receptor type 3 antibody before their incubation with LIF abrogated its effect as did inactivation of LIF by an esterase inhibitor. We also investigated the ability of LIF to stimulate EC to bind untreated PMN. EC were pretreated with LIF (0.25 to 4 U/ml), extensively washed, and adherence measured as before. LIF was shown to induce a dose-dependent increase in the capacity of the EC to bind PMN (from 28.8 +/- 3.1% for untreated EC to 91.1 +/- 4.0% at 4 U LIF; p less than 0.001). Modulation of EC function required a minimum of 30 min and was inhibited in the presence of cycloheximide or actinomycin D. Neither anti-TNF-alpha or -beta antibodies nor polymixin B abrogated the augmentation by LIF. However, anti-IL-1 antibody partially inhibited the stimulation of EC adhesiveness by LIF, suggesting the possible involvement of this cytokine. These studies provide further evidence that LIF may mediate an important pro-inflammatory role in vivo.
Schainberg
H
H
Allergy Division, New England Medical Center, Boston, MA 02111.
Borish
L
L
King
M
M
Rocklin
R E
RE
Rosenwasser
L J
LJ
D002448:Cell Adhesion; D002450:Cell Communication; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D016209:Interleukin-8; D008222:Lymphokines / Q000502:physiology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D010455:Peptides / Q000502:physiology*; D011951:Receptors, Complement / Q000276:immunology; D017463:Receptors, Complement 3b; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D007375:Interleukin-1; D016209:Interleukin-8; D008222:Lymphokines; D010455:Peptides; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D014409:Tumor Necrosis Factor-alpha; C010598:leukocyte inhibitory factor