Endothelium-derived prostaglandin I PGI(2) decreases migration of eosinophils and may be a therapeutic target

Enhanced eosinophil migration from the blood into the tissue is a hallmark of allergic diseases. Prostaglandin (PG) I(2) is the major prostanoid released by endothelial cells.

PGI(2) attenuated the migration of eosinophils through cell-free filters.

The inhibitory effect of PGI(2) on eosinophils was prevented by the IP antagonist Cay10441 and the adenylyl cyclase inhibitor SQ22536.

Similarly, PGI(2) prevented the adhesion of eosinophils to fibronectin and the upregulation and activation of the adhesion molecule CD11b.

Endothelium-derived PGI(2) might be fundamental for the maintenance of the endothelial barrier function against infiltrating cells. Selective IP agonists might have beneficial effects in allergic inflammation.

Mast cells quickly generate different mediators from the metabolism of arachidonic acid: leukotrienes and prostaglandins (LTC4, LTB4, PGD2). These substances are produced within minutes of IgE-receptor crosslinking on the surface of mast cells.

Eicosanoid synthesis. Image source: Wikipedia.

Eicosanoids are signaling molecules made by oxygenation of 20-carbon essential fatty acids. There are 4 families of eicosanoids (PP-LT): prostaglandins (PG), prostacyclins (PGI), leukotrienes (LT) and thromboxanes (TX).

Arachidonic acid. Image source: Wikipedia.


LTC4 is a cysteinyl leukotriene, as are D4 and E4. Image source: Wikipedia.

LTB4. Note the four double bonds, three of them conjugated. This is a common property of A4, B4, C4, D4, and E4. Image source: Wikipedia.

Prostaglandin D2. Image source: Wikipedia.

What is the most potent bronchoconstrictor?

(A) LTB4

(B) LTC4

(C) acetylcholine

(D) histamine

(E) thromboxane A2 (TXA2)

(F) methacholine

Answer: B

CysLTs are the most potent bronchoconstrictor agents yet discovered, about 100-1000 times more potent than histamine. The second most potent bronchoconstrictor is thromboxane A2 (TXA2).

Cysteinyl‐LTs and LTB4 are, respectively, the most potent bronchoconstrictor agents and one of the most effective leukocyte chemotaxins yet.

References:
http://www.ncbi.nlm.nih.gov/pubmed/20153037?dopt=Abstract

Mast Cells and Basophils