Activation of macrophages

Tabata, Y. and Ikada, Y., Activation of macrophage in vitro to acquire antitumor activity by a muramyl dipeptide derivative encapsulated in microspheres composed of lactide copolymer, J Control. Rel.. 6, 189, 1987. 

At cellular level each stage of atheroma development is accompanied by the expression of specific glycoproteins by endothelial cells which mediate the adhesion of monocytes and T-lymphocytes. Their recruitment and migration is triggered by various cytokines released by leukocytes and possibly by smooth muscle cells. Atheroma development continues with the activation of macrophages, which accumulate lipids and become, together with lymphocytes, so-called fatty streaks. The continuous influx, differentiation and proliferation finally leads to more advanced lesion and to the formation of the fibrous plaque. ... 

RAJAVASHISTH T B, YAMADA H and MiSHRA N K (1995) Transcriptional activation of macrophage stimulating factor gene by minimally modified LDL Arteriosclerosis, Thrombosis and Vascular Biology 15, 1591-8. 

As with UC, the immune activation seen in CD involves the release of many proinflammatory cytokines. Cytokines thought to play major roles in CD are derived from T-helper type 1 cells and include interferon-y, TNF-a, and IL-1, IL-6, and IL-12. TNF-a is a major contributor to the inflammatory process seen in CD. Its physiologic effects include activation of macrophages, procoagulant effects in the vascular endothelium, and increases in production of matrix metallo-proteinases in mucosal cells.9,15 Excessive production of both... 

DL-10 (35) T cell, fibroblast Suppression of B- and T-cell proliferation. Inhibition of LPS-induced monocyte IL-1, IL-8, and TNF production. Induction of IL-lra. Suppression of free radical release and NO-dependent microbicidal activity of macrophages. 

Seeley, K.R., andWeeks-Perkins, B.A., Altered phagocytic activity of macrophages in oyster toadfish from a highly polluted subestuary, J. Aquat. Animal Health, 3, 224, 1991. 

Nierkens, S. et al., The reactive d-glucopyranose moiety of Streptozotocin is responsible for activation of macrophages and subsequent stimulation of CD8(+) T Cells. Chem. Res. Toxicol., 18, 872, 2005... 

Fibronectin is an extracellular matrix protein that mediates a variety of cellular effects. It is important in cell-cell and cell-substratum interactions ( 3.9), mediates reticuloendothelial cell activity and binds both to Clq (the first component of complement) and to bacteria. It also increases the tu-mouricidal activity of macrophages and activates complement receptors, by regulating the binding of C3b-coated particles to neutrophils. It may mediate attachment of Staphylococcus aureus to neutrophils and may also play a role as an adhesion factor, promoting the adhesion of neutrophils to surfaces. Fibronectin mRNA (8.7-8.8 kb) is detected only at low levels in... 

Murad, JM., Calvi. SA., Soares, AMVC., Bankova, V. and Sforcin, JM. (2002) J. Ethnopharmacol., Effects of propolis from Brazil and Bulgaria on fungicidal activity of macrophages against Paracoccidiodes brasiliensis, 79, 331-334. 

Tumor Necrosis Factor There are two types of tumor necrosis factor TNF-a and TNF- 8. Of the two, TNF-a has been studied in more detail. TNF-a is a 157 amino acid polypeptide. It is a mediator of immune regulation, including the activation of macrophages and induction of the proliferation of T cells. Another TNF-a function is its cytotoxic effects on a number of tumor cells. Recent research, however, concentrates on its property in the stimulation of inflammation, particularly in the case of rheumatoid arthritis. Clinical trials are being conducted with drugs to block TNF-a with anti-TNF-a monoclonal antibodies. These antibodies target the excessive levels of TNF-a in the synovial fluid of joints and provide relief to sufferers of rheumatoid arthritis (Exhibit 4.10). 

Krishnan L, et al. The potent adjuvant activity of archaeosomes correlates to the recruitment and activation of macrophages and dendritic cells in vivo. J Immunol 2001 166 1885. 

Mode of action Activation of macrophages/monocytes release of endogenous mediators such as lipids from arachidonic acid, reduced oxygen species, proteins 1. Pore formation in cell membranes 2. Enzymatic modification of specific substrates in the cytosol of host cells (AB-type toxins) 3. Superantigen stimulation of the immune system... 

Other information on the immunotoxicity of chloroform is limited to one study on effects of chloroform on host resistance in CD-I mice. A single exposure to 10.6 ppm chloroform for 3 hours did not increase the mortality rate after streptococcal challenge and did not alter the ability of alveolar macrophages to destroy bacteria in these mice (Aranyi et al. 1986). After repeated chloroform exposure (3 hours a day for 5 days), the mortality rate significantly increased, but the bactericidal activity of macrophages was not suppressed compared to control animals. 

A number of factors increase the risk of disruption of the plaque the presence of a considerable amount of fat in the plaque the effects of physical stress on the vessel wall, particularly in the hypertensive patient and the activity of macrophages. Macrophages release proteases (e.g. colla-genase, elastase) which lead to breakdown of the plaque. Rupture of the plaque produces fissures that are sites for aggregation of platelets. Fragments from the rupture can occlude blood vessels. 

Encapsulation of immunomodulators, e.g. muramyl tripeptide analogues, into liposomes has been designed to stimulate host immunity [108] and can be used in combination with other treatment modalities. The systemic activation of macrophages provides an additional therapeutic modality for the eradication of cancer and cancer metastases. 

A3. Adam, P., Lipophagocytic activity of macrophages. Czech Neurol. Neurosurg. 56/89(4), 170-171,(1993). 

The type of inhibition of chicken intestine alkaline phosphatase by forphenicine was not competitive, but uncompetitive with the stibstrate. Its derivative, forphenicinol, which contains a hydroxymethyl grorp instead of the formyl group in the forphenicine molecule, did not inhibit alkaline phosphatase but, it did bind to cells. Forphenicinol enhanced delayed-type lOT>ersensiti-vity (13,14) and the phagocytic activity of macrophages. 

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