scholarly journals Role of membrane oxidation in controlling the activity of human group IIa secretory phospholipase A2 toward apoptotic lymphoma cells

2013 ◽  
Vol 1828 (2) ◽  
pp. 670-676 ◽  
Author(s):  
Elizabeth Gibbons ◽  
Jennifer Nelson ◽  
Lynn Anderson ◽  
Kelly Brewer ◽  
Stephanie Melchor ◽  
...  
2012 ◽  
Vol 102 (3) ◽  
pp. 628a-629a
Author(s):  
Elizabeth Gibbons ◽  
Lynn Anderson ◽  
Kelly Damm ◽  
Stephanie Melchor ◽  
Jennifer Nelson ◽  
...  

2002 ◽  
Vol 365 (2) ◽  
pp. 505-511 ◽  
Author(s):  
Chang-Zhi DONG ◽  
Anthony ROMIEU ◽  
Carine M. MOUNIER ◽  
Françoise HEYMANS ◽  
Bernard P. ROQUES ◽  
...  

Human group IIA secretory phospholipase A2 (hGIIA sPLA2) is reported to be involved in inflammation, since its expression level is enhanced under various inflammatory conditions. In this work, we report the total chemical synthesis of this enzyme (124 amino acids) by solid-phase method. The identity of the protein, in denatured or folded (7 disulphide bonds) forms, was confirmed by electrospray MS. Synthetic sPLA2 possesses the same circular dichroism spectrum, enzymic activity in hydrolysing different phospholipid substrates, and inhibitory effect in thrombin formation from prothrombinase complex as the recombinant sPLA2. Furthermore, LY311727, a reported specific hGIIA sPLA2 inhibitor, is able to inhibit the synthetic and the recombinant enzymes with the same efficiency. This study demonstrates that chemically continuous solid phase synthesis is an alternative and less time-consuming approach to producing small, structurally folded and fully active proteins of up to 124 amino acids, such as hGIIA sPLA2. Moreover, this technique provides more flexibility in analogue synthesis to elucidate their physiological functions and pathological effects.


Blood ◽  
2005 ◽  
Vol 105 (9) ◽  
pp. 3583-3587 ◽  
Author(s):  
Reinhold Ramoner ◽  
Thomas Putz ◽  
Hubert Gander ◽  
Andrea Rahm ◽  
Georg Bartsch ◽  
...  

Abstract Dendritic cells (DCs), also referred to as the sentinels of the immune system, induce and coordinate important functions of immune surveillance. DCs acquire immunity-initiating capacity only after a process of maturation usually induced by ligands that bind to members of the tumor necrosis factor (TNF) or toll-like receptor families. Secretory phospholipase A2 (sPLA2), which hydrolyzes the sn-2 ester bond of glycerophospholipids, regulates a variety of cellular functions including migration of endothelial cells and neurite outgrowth. In the present study we investigated the role of sPLA2 in DC biology. We report that human monocyte-derived DC cultures lack sPLA2 activity but respond to exogenous sPLA2. sPLA2 alone and in cooperation with TNF-α and interleukin 1 β (IL-1β) induced fatty acid release from DC membranes, which was accompanied by upregulation of surface markers and by an increase in the migratory and immunostimulatory capacity of the DCs. Our findings indicate that secreted enzymes such as sPLA2 can contribute to DC maturation and emphasize the role of lipid mediators in the regulation of immune responses. This observation may also have implications for DC-based vaccine development.


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