Tumor necrosis factor-␣ (TNF-␣) and interleukin-1␤ (IL-1␤), essential components in the pathogenesis of immunoinflammatory diseases, are strongly induced in monocytes by direct contact with stimulated T lymphocytes. This study demonstrates that adult human serum (HS) but not fetal calf or cord blood serum displays inhibitory activity toward the contact-mediated activation of monocytes by stimulated T cells, decreasing the production of both TNF-␣ and IL-1␤. Fractionation of HS and N-terminal microsequencing as well as electroelution of material subjected to preparative electrophoresis revealed that apolipoprotein A-I (apo A-I), a "negative" acute-phase protein, was the inhibitory factor. Functional assays and flow cytometry analyses show that highdensity lipoprotein (HDL)-associated apo A-I inhibits contact-mediated activation of monocytes by binding to stimulated T cells, thus inhibiting TNF-␣ and IL-1␤ production at both protein and messenger RNA levels. Furthermore, apo A-I inhibits monocyte inflammatory functions in peripheral blood mononuclear cells activated by either specific antigens or lectins without affecting cell proliferation. These results demonstrate a new antiinflammatory activity of HDL-associated apo A-I that might have modulating functions in nonseptic conditions. Therefore, because HDL has been shown to bind and neutralize lipopolysaccharide, HDL appears to play an important part in modulating both acute and chronic inflammation. IntroductionTumor necrosis factor-␣ (TNF-␣) and interleukin-1␤ (IL-1␤) are strongly induced in monocytes by direct contact with stimulated T lymphocytes, both cells involved in immunoinflammatory diseases such as rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, and atherosclerosis. The importance of TNF-␣ and IL-1 in chronic inflammation has been well established. Based on the premise that T lymphocytes play a pivotal role in the pathogenesis of chronic inflammatory diseases, we demonstrated that direct cell-cell contact with stimulated T lymphocytes is a major stimulus triggering the production of large amounts of TNF-␣ and IL-1␤ in monocytes. [1][2][3] Various stimuli are able to induce T cells to activate monocytes by direct cellular contact: (1) mitogens, for example, a combination of phytohemagglutinin (PHA) and phorbol myristate acetate (PMA), 1,4-6 (2) cross-linking of CD3 by immobilized anti-CD3 monoclonal antibody (mAb) with or without cross-linking of the costimulatory molecule CD28, 7,8 (3) antigen-recognition on antigen-specific T-cell clones, 8 and (4) cytokines. 9 The identity of the ligands on plasma membrane of stimulated T cells that trigger the signaling of monocytemacrophages as well as that of the counter-ligands on monocytes is still elusive. However, in the human system some of the signaling may be attributed to ␤ 2 -integrins, CD69, CD23, CD40-CD40L and lymphocyte activation gene-3 (LAG-3). 1,4,5,10-14 Membrane-associated TNF-␣ and IL-1 do not play a crucial part in this cellular interaction, contrasting with their sign...

Polarized expression of most epithelial plasma membrane proteins is achieved by selective transport from the Golgi apparatus or from endosomes to a specific cell surface domain. In Madin-Darby canine kidney (MDCK) cells, basolateral sorting generally depends on distinct cytoplasmic targeting determinants. Inactivation of these signals often resulted in apical expression, suggesting that apical transport of transmembrane proteins occurs either by default or is mediated by widely distributed characteristics of membrane glycoproteins. We tested the hypothesis of Nlinked carbohydrates acting as apical targeting signals using three different membrane proteins. The first two are normally not glycosylated and the third one is a glycoprotein. In all three cases, N-linked carbohydrates were clearly able to mediate apical targeting and transport. Cell surface transport of proteins containing cytoplasmic basolateral targeting determinants was not significantly affected by N-linked sugars. In the absence of glycosylation and a basolateral sorting signal, the reporter proteins accumulated in the Golgi complex of MDCK as well as CHO cells, indicating that efficient transport from the Golgi apparatus to the cell surface is signal-mediated in polarized and non-polarized cells.

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Comparison of the features of arthroscopic synovial biopsies with biopsy samples obtained at surgery