Characterization and Expression Kinetics of an Endothelial Cell Activation Antigen Present in vivo Only in Acute Inflammatory Tissues

Abstract

Endothelial cell activation by endotoxin (LPS), tumor necrosis factor (TNF), Interleukin-1-α, β (IL-1-α β) and phorbolesters (TPA) results in increased monocyte adhesion. Examination of kinetics of monocyte adhesion shows that the onset of adherence enhancement (AE) is similar in all five agents (about 300% AE at 6 h), while its decrease is delayed in LPS/TNF versus IL-1-α, β /TPA-induced activation (LPS versus IL-1- β:260% versus 60% at 18 h). Monoclonal antibody (4D10), raised against 24 h LPS-stimulated endothelial cells detects an endothelial cell-specific activation antigen at M_r 81,000 that is induced by LPS, TNF, IL-1-α β and TPA (within 6 h about 100% positive cells). Decrease in antigen-positive cells is delayed in LPS/TNF versus IL-1-α, β /TPA-induced antigen expression (LPS vs. IL-1-β: 60% vs. 5% at 24 h). In situ the antigen is not expressed in normal and chronic inflammatory tissues. Acute inflammatory tissues, including contact and atopic dermatitis, psoriasis and periodontitis, however, show endothelial cells staining strongly positive. In contact eczemas at different times after elicitation (0, 6, 24, 72, 96 h), expression of the antigen is first seen after 24 h and is still strong at 96 h. These data indicate that LPS/TNF conduct an endothelial cell activation program in vitro, showing the same prolonged kinetics that is found for endothelial cell activation in the acute inflammatory process in vivo.

Differential Adherence of the Human Monocyte Subsets 27E10 and RM3/1 to Cytokine- or Glucocorticoid-Treated Endothelial Cells

“…The decrease in ELAM-1, however, depends on the mediator used. With TNFa ELAM-1 remains elevated 30% above the base val ue after 24 h [8]. It has been shown by Hakkert et al [9] that monocyte adherence to stimulated HUVECs (4 h with IL-1P) is reduced only by about 30% by mAbs against ELAM-1.…”

“…It has been shown by Hakkert et al [9] that monocyte adherence to stimulated HUVECs (4 h with IL-1P) is reduced only by about 30% by mAbs against ELAM-1. This suggests that ELAM-1 does not play an important role in monocyte adherence although Goerdt et al [8] showed a strong increase in monocyte adherence to ELAM-1-expressing HUVECs. Mediation of neutrophilic adhesion seems to be the main role of ELAM-1 since the expression of ELAM-1 correlated with the influx of neutrophilic granulocytes [7].…”

“…These are VCAM-1, ICAM-1, ELAM-1, the integrin a4 pi (VLA-4), and y-IP-10. The counter receptors so far characterized on monocytes are: LFA-1, Mac-1, and p i 50,95 [1,2,11,15,17,18], ELAM-1 is not expressed in unstimulated HUVECs but it is rapidly and transiently inducible by IL-lp and TNFa but not by IFNy, with peak values after 4-6 h and followed by a quick decrease [8,11]. The decrease in ELAM-1, however, depends on the mediator used.…”

“…Cytokines like IL-1, interferon-y (IFNy), and TNFa are known to modulate the expression of endothelial adhe sion molecules, particular of ELAM-1, VCAM-1, and ICAM-1 [7][8][9][10][11][12], The present experiments were designed to elucidate the modulating role of IL-lß, IL-6, TNFa, IFNy, and the glucocorticoid prednylidene (Pred) for the adherence of different monocyte/macrophage phenotypes to human umbilical vein endothelial cells after a 24-hour incubation period.…”

Characterization and Differential Expression of an Endothelial Cell-Specific Surface Antigen in Continuous and Sinusoidal Endothelia, in Skin Vascular Lesions and in vitro

“…In contrast to the average continuous endothe lial cell antigenicity, splenic sinusoidal endo thelial cells express Leu-2 [Turner et al, 1986;Buckley et al, 1985;Buckley and Dickson, 1984] and the transferrin receptor OKT 9 [Buckley et al, 1985], and lack HC1 [Posnett et al, 1984;Rutgers et al, 1986;Scully et al, 1988] and B721 [Voland et al, 1987;Scully et al, 1988]; liver sinusoidal endothelial cells express Leu M3 [Turner et al, 1986], 63D3 and 61D3 [Turner et al, 1986;Ugolini et al, 1980] and lack von-Willebrand antigen I and II, HC1 and B721, renal glomerular endothelial cells lack vonWillebrand antigen I and II. HLA-DR anti gens, OKM 5 [Knowles II et al, 1984] and B721, and acute inflammatory endothelial cells in addition express the putative leuko cyte adhesion molecules H4/18 [Pober et al, 1986] and 4D10 [Goerdt et al, 1987] and the C3b receptor To5 [Smiley et al, 1985;Gerdes et al, 1981;Ryan et al, 1981]. Minor differences are seen, e.g.…”