CD74 (also known as a MHC class II invariant chain) is a type II transmembrane cookoo watch price pr

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The electronic version of this article is the complete cookoo watch price one and can be found online at: http://respiratory-research.com/content/10/1/33 Received: 4 March 2009 Accepted: 4 May 2009 Published: 4 May 2009
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MIF is a critical mediator of the host defense, and is involved in both acute and chronic responses in the lung. Neutralization of MIF reduces neutrophil accumulation into the lung in animal models. We hypothesized cookoo watch price that MIF, in the alveolar space, promotes neutrophil accumulation via activation of the CD74 receptor on macrophages. Methods
To determine whether macrophage CD74 surface expression contributes MIF-induced neutrophil accumulation, we instilled recombinant MIF (r-MIF) cookoo watch price into the trachea of mice in the presence or absence of anti-CD74 antibody or the MIF specific inhibitor, ISO-1. Using macrophage cookoo watch price culture, we examined the downstream pathways cookoo watch price of MIF-induced activation that lead to neutrophil accumulation. Results
Intratracheal instillation of r-MIF increased the number of neutrophils as well as the concentration of macrophage inflammatory protein 2 (MIP-2) and keratinocyte-derived chemokine (KC) in BAL fluids. CD74 was found to be expressed on the surface of alveolar macrophages, and MIF-induced MIP-2 accumulation was dependent on p44/p42 MAPK in macrophages. Anti-CD74 antibody inhibited MIF-induced p44/p42 MAPK phosphorylation and MIP-2 release by macrophages. Furthermore, we show that anti-CD74 antibody inhibits MIF-induced alveolar accumulation of MIP-2 (control IgG vs. CD74 Ab; 477.1 136.7 vs. 242.2 102.2 pg/ml, p < 0.05), KC (1796.2 436.1 vs. 1138.2 310.2 pg/ml, p < 0.05) and neutrophils (total number of neutrophils, 3.33 0.93 10 4 vs. 1.90 0.61 10 4 , p < 0.05) in our mouse model. Conclusion
MIF-induced neutrophil accumulation in the alveolar space results from interaction with CD74 expressed on the surface of alveolar macrophage cells. This interaction cookoo watch price induces p44/p42 MAPK activation and chemokine release. The data suggest that MIF and its receptor, CD74, may be useful targets to reduce neutrophilic lung inflammation, and acute lung injury. Background
Macrophage migration inhibitory factor (MIF) is an inflammatory mediator of innate and adaptive immune responses. MIF protein is present in most cells including pituitary cells, cookoo watch price T cells, macrophages/monocytes, and is released in response to infection and stress [ 1 ]. Plasma MIF concentrations are elevated in patients with inflammatory diseases such as sepsis [ 2 ], ARDS [ 3 , 4 ] or rheumatoid arthritis [ 5 ]. In addition, plasma concentration of MIF is positively correlated with the severity of sepsis [ 6 , 7 ]. Furthermore, cookoo watch price mice deficient in the MIF gene, or those in which the MIF protein has been neutralized, are protected from lethal endotoxemia and septic shock [ 8 , 9 ].
In lung inflammation and injury models, MIP-2 and KC play key roles in neutrophil accumulation into the lungs [ 10 ]. Neutrophils are an important component of the inflammatory response in acute lung injury [ 11 , 12 ]. The elimination of neutrophils can markedly decrease the severity of lung injury in animal lung inflammation cookoo watch price models [ 13 ]. MIF levels are increased cookoo watch price in BAL fluid in lipopolysaccharide (LPS)-induced cookoo watch price lung injury model [ 14 ], and MIF neutralizing cookoo watch price antibody blocks LPS-induced pulmonary neutrophil accumulation in animal models [ 15 , 16 ], suggesting that MIF can influence neutrophil accumulation cookoo watch price into the lungs.
CD74 (also known as a MHC class II invariant chain) is a type II transmembrane cookoo watch price protein, reported to be part of the MIF receptor complex [ 17 ]. Several studies have shown that CD74 is expressed both intracellularly and on the cell surface in B cell lymphoma [ 18 ], T cell lymphoma, cookoo watch price melanoma cells [ 19 ] and gastric epithelial cells [ 20 ]. MIF binds to cell surface CD74, and induces p44/p42 MAPK phosphorylation and cell proliferation. Moreover neutralization of CD74 inhibits MIF-induced cookoo watch price cell proliferation in B cells and fibroblasts cookoo watch price [ 17 ]. Other recent studies have shown that anti-CD74 antibody blocks MIF-CD74 binding on the cell surface of gastric epithelial cells [ 21 ], and anti-CD74 a