"New & former GREMI Presidents"
The new GREMI's president Mustapha Si-Tahar has been elected by the General Assembly on March 2015. All the GREMI members would like to thank the former Michel Chignard for his dynamic and very friendly direction of the association for the last 13 years.


The team of Véronique Witko-Sarsat, in collaboration with the Department of Internal Medicine, have demonstrated a new driver in a pathway that promotes inflammation in a particular type of autoimmune vasculitis called the granulomatosis with polyangiitis. The dual role of neutrophil proteinase 3 in autoimmune vasculitis: when an autoantigen become a danger signal for the immune system. The Journal of Clinical Investigation
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Last update April 2015


The classical features of inflammatory reactions are 1) an increase in blood flow, 2) an increase in vascular permeability with migration of cells into the tissue compartment, 3) the release of factors at the tissue sites and 4) resolution. These events are associated with a variety of locally released mediators which activate specific receptors. There is now considerable evidence to suggest that metabolites of the arachidonic acid cascade, namely, prostanoids, leukotrienes and lipoxins play a substantial role in the different phases of inflammation.

            The biological actions of arachidonic acid have essentially been attributed to the conversion of this substrate to a number of metabolites. The release of these lipid mediators varies considerably and depends to a large extent on the specific cell which is activated. Often several cells may interact to produce these lipid mediators by sharing the substrate and/or enzymes responsible for metabolite formation.

A series of enzymatic pathways, namely, cyclooxygenases (COX1, COX2) and lipoxygenases are responsible for the formation of numerous lipid mediators known as eicosanoids. The former enzymes are responsible for the formation of prostaglandins and thromboxane whereas the lipoxygenases transform arachidonic acid to the leukotrienes. The dual lipoxygenation of arachidonic acid by either the 15-lipoxygenase and the 5-lipoxygenase or the 12-lipoxygenase and the 5-lipoxygenase produce eicosanoids known as lipoxins. One of the oxoeicosanoids, the metabolite 5-oxo-6,8,11,14-eicosatetraenoic acid, which is derived from the activity of 5(S)-hydroxyeicosanoid dehydrogenase, has recently been shown to also be a potent mediator during inflammation. All of these endogenous lipid mediators are known to produce their biological effects by activation of specific cloned receptors.

            The evolution of eicosanoid receptors have now been phylogenically analyzed based on amino acid sequences. These receptors are located on a variety of cells, tissues, and organs and can be activated by either selective or non-selective ligands. Several of the receptors are known to play a role in different physiological conditions, for example: the control of the vascular tone. However, during chronic inflammation, such as, asthma, atherosclerosis, rheumatoid arthritis and gastrointestinal disease, their over-expression and role has yet to be fully elucidated. Of considerable interest are the number of compounds which have been developped and are known to selectively antagonized these receptors. In fact a few of the antagonists have been shown to be effective therapeutic agents.


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