Specific Activation of Leukocyte β2 Integrins Lymphocyte Function–associated Antigen-1 and Mac-1 by Chemokines Mediated by Distinct Pathways via the α Subunit Cytoplasmic Domains

We show that CC chemokines induced a sustained increase in monocyte adhesion to intercellular adhesion molecule-1 that was mediated by Mac-1 (αMβ2) but not lymphocyte function–associated antigen-1 (LFA-1; αLβ2). In contrast, staining for an activation epitope revealed a rapid and transient up-regulation of LFA-1 activity by monocyte chemotactic protein-1 (MCP-1) in monocytes and Jurkat CCR2 chemokine receptor transfectants or by stromal-derived factor-1α in Jurkat cells. Differential kinetics for activation of Mac-1 (sustained) and LFA-1 (transient) avidity in response to stromal-derived factor-1α were confirmed by expression of αM or αL in αL-deficient Jurkat cells. Moreover, expression of chimeras containing αL and αM cytoplasmic domain exchanges indicated that α cytoplasmic tails conferred the specific mode of regulation. Coexpressing αM or chimeras in mutant Jurkat cells with a “gain of function” phenotype that results in constitutively active LFA-1 demonstrated that Mac-1 was not constitutively active, whereas constitutive activity was mediated via the αL cytoplasmic tail, implying the presence of distinct signaling pathways for LFA-1 and Mac-1. Transendothelial chemotaxis of monocytes in response to MCP-1 was dependent on LFA-1; however, Mac-1 was involved at MCP-1 concentrations stimulating its avidity, showing differential contributions of β2 integrins. Our data suggest that a specific regulation of β2 integrin avidity by chemokines may be important in leukocyte extravasation and may be triggered by distinct activation pathways transduced via the α subunit cytoplasmic domains.

Phorbol-12-myristate-13-acetate induces nociceptin in human Mono Mac 6 cells via multiple transduction signalling pathways.

BACKGROUND Nociceptin in the peripheral circulation has been proposed to have an immunoregulatory role with regards to inflammation and pain. However, the mechanisms involved in its regulation are still not clear. The aim of this study was to investigate signalling pathways contributing to the regulation of the expression of nociceptin under inflammatory conditions. METHODS Mono Mac 6 cells (MM6) were cultured with or without phorbol-12-myristate-13-acetate (PMA). Prepronociceptin (ppNOC) mRNA was detected by RT-qPCR and extracellular nociceptin by fluorescent-enzyme immunoassay. Intracellular nociceptin and phosphorylated kinases were measured using flow cytometry. To evaluate the contribution of various signalling pathways to the regulation of ppNOC mRNA and nociceptin protein, cells were pre-treated with specific kinase inhibitors before co-culturing with PMA. RESULTS ppNOC mRNA was expressed in untreated MM6 at low concentrations. Exposure of cells to PMA upregulated ppNOC after nine h compared with controls without PMA (median normalized ratio with IQR: 0.18 (0.15-0.26) vs. 0 (0-0.02), P<0.01). Inhibition of mitogen-activated protein kinases specific for signal transduction reversed the PMA effects (all P<0.001). Induction of nociceptin protein concentrations in PMA stimulated MM6 was prevented predominantly by identity of ERK inhibitor (P<0.05). CONCLUSIONS Upregulation of nociceptin expression by PMA in MM6 cells involves several pathways. Underlying mechanisms involved in nociceptin expression may lead to new insights in the treatment of pain and inflammatory diseases.

Ponts et ouvrages en maçonnerie /

Mode of access: Internet.

Les Francs-maçons et les sociétés secrétes

Mode of access: Internet.

Le maçon : opéra français /

Mode of access: Internet.

Manuel complet de médecine légale, ou résumé des meilleurs traités anciens et modernes, particulièrement de ceux de Mahon et de M. Fodéré /

Mode of access: Internet.

Carta polémica dirigida desde Mahon al redactor del Diario Complementario del Diccionario de las Ciencias Medicas en Paris, en refutacion de un articulo del espresado diccionario, no solamente por ser falso en todas sus partes, sino injurioso á la ilustracion española en general y particularmente á su cirujía y medicina militar /

Mode of access: Internet.

Dissertatio de raro ventriculi casu cum vera morbi diagnosi / quam a perillustri viro, Guilielmo Mac-Neven o Kelly ab Aghrim ... in exercitationem academicam propositam, in magna Aula Carolina Almae Universitatis Pragensis defendit Franciscus Mitterbacher.

Mode of access: Internet.

Historia Civil, y natural de la isla de Menorca : descripción topografica de la ciudad de Mahon y demás poblaciones /

Mode of access: Internet.

Catalogue des livres rares et précieux de la bibliothèque de feu M. le comte de Mac-Carthy Reagh.

"Notice abrégée des livres impriḿs¯ sur vélin" : v. 2, p. [259]-289 (601 entries)

Les plus secrets mystères des hauts grades de la maçonnerie dévoilés, ou, Le vrai Rose-Croix /

Mode of access: Internet.

Les francs-maçons plaideurs.

Mode of access: Internet.

Les juifs d'Europe et de Palestine : voyage de MM. Keith, Black, Bonar et Mac Cheyne, envoyés par l'Église d'Écosse /

Includes index.