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Articular inflammation induced by phospholipases A2-IIa group: characterization of histophatologic and eletrophysiologic alterations and chemical mediation

Grant number: 06/03879-0
Support Opportunities:Regular Research Grants
Duration: December 01, 2006 - April 30, 2009
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Gisele Picolo
Grantee:Gisele Picolo
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil


Phospholipases A2 constitute a family of structurally related proteins that hydrolyze phospholips releasing arachidonic acid, the substrate for the biosynthesis of several mediators of inflammation, such as prostaglandins, prostacyclin, thromboxane and leukotrienes.PLA2s are abundant in different kinds of mammals, principally human, mice and bovine. In addition, they are found in snake, bee and lizard venoms, and in plants and conus snails. Phospholipases A2 characterized as IIA group are abundant in snake venoms from Bothrops genus and several data have shown that phospholipases isolated from these venoms induce inflammation and pain. Inflammation and pain are important symptoms from in many disorders, including arthritis. It is known that high levels of group IIA PLA2s can be found in synovial fluid of patients with rheumatoid arthritis, and the activity of these enzymes can be correlated to the disease severity. However, despite the clinical importance of arthritis, the involvement of PLA2 in the genesis and/or maintenance of articular inflammation is not well characterized. In addition, treatments for this disorder are not totally effective, since there are not experimental models able to reproduce the symptoms of arthritis in humans. The aim of this project is to characterize the articular inflammatory response induced by Lys 49-PLA2 (IIA group) isolated from B. asper snake venom, analyzing the histophatological, inflammatory and eletrophysiological alterations induced by this PLA2 and to determine the chemical mediation and cell activation during inflammatory process, developing a new experimental model of arthritis, trying to better understand the pathophysiology of this disorder and looking for efficient control of articular inflammation. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DIAS, RENATA GONCALVES; SAMPAIO, SANDRA COCCUZZO; SANT'ANNA, MORENA BRAZIL; CUNHA, FERNANDO QUEIROZ; GUTIERREZ, JOSE MARIA; LOMONTE, BRUNO; CURY, YARA; PICOLO, GISELE. Articular inflammation induced by an enzymatically-inactive Lys49 phospholipase A2: activation of endogenous phospholipases contributes to the pronociceptive effect. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 23, n. 1, . (06/03879-0)

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