2,284 research outputs found
Editorial: Gigantism: a new way to prolong neutrophil life
No full textComment on
The development of giant phagocytes in long-term neutrophil cultures. [J Leukoc Biol. 2014
The tyrosine kinase Abl is a component of macrophage podosomes and is required for podosome formation and function.
No full textMyeloid leukocytes form actin-based plasma membrane protrusions, called podosomes, that are implicated in myeloid cell recruitment into tissues and cell migration within the interstitium. In this study we show that tyrosine kinases of the Abl family are present in podosomes formed by murine and human macrophages. Silencing of Abl expression in bone-marrow-derived macrophages and monocyte-derived macrophages by siRNA or Abl enzymatic inhibition with imatinib resulted in the disassembly of macrophage podosomes and the reduction of their capacity to degrade an extracellular matrix and migrate through matrigel matrices and endothelial cell monolayers. Additionally, macrophages deficient in Src-family kinases, which cross-talk with Abl in regulating macrophage migration, also demonstrated podosome disassembly. These findings suggest that podosome disassembly induced by Abl targeting may inhibit podosome-dependent functions such as leukocyte recruitment into inflammatory sites and osteoclast-dependent bone resorption
Superoxide release by peritoneal and bone marrow-derived mouse macrophages. Modulation by adherence and cell activation
No full textMacrophages (M phi) activated by BCG and other immune stimuli differ from thioglycollate-elicited M phi (TPM) in releasing O-2 upon initial contact with a foreign substratum. During adherence and spreading, activated M phi release approximately 50% of O-2 levels triggered by phorbol myristate acetate (PMA). The response requires divalent cations (Ca++ or Mg++) and is sensitive to lignocaine, a reversible inhibitor of adhesion. These features distinguish this reaction from the response to PMA, which also triggers substantial release of O-2 from TPM, 60-80% of bacille Calmette--Guerin-activated peritoneal M phi (BCG-PM) activity. During prolonged cultivation as monolayers, peritoneal and bone marrow derived M phi (BMDM) progressively lose their ability to release O-2 in response to PMA and serum-treated zymosan (STZ), although the cells continue to secrete other products and to phagocytose STZ. This loss can be prevented by maintaining peritoneal and BMDM as non-adherent cells in teflon beakers or poly-(2-hydroxyethylmethacrylate) (poly HEMA) coated vessels. High levels of O-2 activity were observed after cultivating TPM on poly-HEMA (300 nmoles O-2/mg/hr after PMA), 10-fold more than adherent controls. BMDM could be induced to release four-fold more O-2, greater than 100 nmoles O-2/mg/hr, after cultivation as non-adherent cells in the absence of L cell-conditioned medium. Our results show that heterogeneity in M phi respiratory burst activity depends on (i) intrinsic differences between populations, (ii) differential responses by activated and non-activated M phi to selective surface stimuli and (iii) modulation by environmental factors which control adherence and growth
Modulation of macrophage mannosyl-specific receptors by cultivation on immobilized zymosan. Effects on superoxide-anion release and phagocytosis
No full textUnopsonized zymosan effectively induces a respiratory burst (O-2 release, hexose monophosphate (HMP) shunt stimulation) in thioglycollate-elicited and BCG-activated macrophages (M phi). These M phi are known to express lectin-like receptors specific for mannose or fucose-terminated glycoconjugates (MFR). A role for the MFR in phagocytosis of zymosan was demonstrated by cultivating M phi on a glutaraldehyde-fixed layer of zymosan, a procedure which depleted M phi of MFR-mediated pinocytic activity, but not other surface antigens (F4/80, Mac-1) or receptors (FcR, C3R). After modulation of MFR, M phi lost the ability to phagocytose zymosan, but ingested antibody or complement-coated zymosan vigorously via alternative receptors. Challenge with free zymosan failed to enhance respiratory burst activity in M phi which had been cultivated on zymosan. Such M phi were also refractory to zymosan taken up by alternative receptors or other ingested particles (EIgG), but responded to a non-particulate challenge, PMA. These studies show that the MFR, like other receptors, can mediate phagocytosis and elicit a respiratory burst in suitably primed M phi, but indicate that phagocytosis via specific receptors (FcR, C3R) need not trigger a respiratory burst
Desensitization of macrophages to stimuli which induce secretion of superoxide anion. Down-regulation of receptors for phorbol myristate acetate
No full textThe ability of cultivated mouse peritoneal macrophages (M phi) to release superoxide anion (O-2) after repeated stimulation by phorbol myristate acetate (PMA) or serum-treated zymosan (STZ) has been studied. After a maximal first stimulus bacillus Calmette-Guerin (BCG)-activated M phi released high levels of O-2, 2-fold more than thioglycollate-elicited M phi and the response ceased within 4 h. Both populations either responded again to a second challenge or displayed a refractory state which varied in duration and selectivity. Desensitization by STZ pretreatment was transient and selective whereas PMA could render M phi refractory for 3 days to PMA alone or to both agents, depending on the amount of PMA used and the conditions of stimulation. PMA induced a selective loss of specific saturable receptors for [3H]phorbol dibutyrate, a closely related agent, and receptor activity recovered with the ability to release O-2. Loss of receptors did not account for concomitant loss of the response to STZ after nonselective deactivation. Such M phi were fully viable and able to endocytose various soluble and particulate ligands vigorously, but without stimulation of the hexose monophosphate shunt or release of O-2. Our studies indicate that M phi activities can be profoundly altered by prior stimulation, that specific receptors play a role in ligand-induced desensitization and that agents such as PMA can selectively eliminate the cells' ability to generate a second respiratory burst
Desativar o direito: um caminho a partir da obra de Giorgio Agamben
Get PDFDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Jurídicas, Programa de Pós-Graduação em Direito, Florianópolis, 2014O trabalho parte do problema de tentar pensar uma forma de resistência pelo Direito. A hipótese sustentada encontra amparo na noção de "desativar" o Direito, contida na obra de Giorgio Agamben. Neste sentido, o trabalho busca recompor os paradigmas jurídico-político e governamental dentro da obra do autor em questão, principalmente a partir dos livros "O poder soberano e a vida nua", "Estado de Exceção" e "O Reino e a Glória". Ao fim, a proposta de "desativar" o Direito e o conceito de inoperosidade defrontam-se com a máquina governamental agambeniana. Na conclusão, a filosofia do Direito é apresentada como alternativa para se pensar uma nova relação entre Direito e vida.Abstract: The work begins from the problem of trying to think of a way of resistance by Law. The hypothesis is supported by the notion of "deactivate" the law, contained in the work of Giorgio Agamben. In this sense, this dissertation seeks to reconstruct the legal-political and governmental paradigms within the work of the author in question, mostly from the books "The sovereign power and bare life", "State of Exception" and "The Kingdom and the Glory". At the end, the proposal to "deactivate" the Law and the concept of unindustriousness are confronted with Agamben's government machinery. In conclusion, the philosophy of law is presented as an alternative to think about a new relationship between law and life
Desensitization of macrophage oxygen metabolism on immobilized ligands: different effect of immunoglobulin G and complement
No full textDuring adhesion and spreading to immobilized immune complexes, casein-elicited mouse peritoneal macrophages produced superoxide anion. This production was time-dependent, ceased after a couple of hours, and was due to interaction with immunoglobulins G (IgG) because neither immobilized antigen alone nor immunoglobulins M with or without complement-derived fragments were efficient stimuli. Cultivation of macrophages on immobilized IgG for 24 hr caused desensitization of the response to an unrelated stimulus like zymosan. Desensitization was due neither to inhibition of binding and uptake of zymosan nor to alterations of NADPH oxidase. In fact, macrophages cultivated on immobilized IgG bound and internalized zymosan and responded to PMA with production of superoxide anion normally. Desensitization was not specific for casein-elicited macrophages because both resident peritoneal and Corynebacterium parvum-activated macrophages underwent desensitization if cultivated for 24 hr on immobilized immune complexes. Desensitization on immobilized IgG was maximal after 24 hr, lasted up to 3 days in culture, and was reversed by detaching macrophages from the IgG surface and further cultivating them in normal tissue culture plastic. Scavengers of products of the oxygen metabolism such as superoxide dismutase and catalase and inhibitors of arachidonic acid metabolism such as indomethacin and nordihydroguaiaretic acid did not prevent desensitization. In addition, the zymosan-stimulated release of arachidonic acid was suppressed after cultivation on immobilized IgG for 24 hr; also in this case, the response to PMA was conserved. Contrary to cultivation on immobilized IgG, cultivation of macrophages on fragments derived from C3 was not accompanied by desensitization of the response to zymosan. These results indicate that although the interaction of Fc receptors with their ligands does not impair binding and uptake of zymosan, alterations in the sequence of signals which leads to the activation of the oxygen metabolism can occur, causing a complete dissociation between phagocytosis and stimulation of the oxygen metabolism
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