Leukotriene B(4)-BLT1 axis may contribute to airway remodeling in asthma

Leukotriene B(4) (LTB(4)) increases in induced sputum and exhaled breath condensate in people with asthma. However, the direct effects of LTB(4) on human airway smooth muscle (ASM) have not been studied.

A recent study suggested a role for a LTB(4)-BLT1 signaling axis in ASM responses that may contribute to airway remodeling in asthma.

LTB(4) induced cyclin D1 expression, proliferation, and chemokinesis of human ASM cells. LTB(4) also induced phosphorylation of both p42/p44 mitogen-activated protein kinase (MAPK) and downstream PI3 kinase effector, Akt1 (hyperlinks from Wikipedia).


Mast cells (mind map).


Eicosanoid synthesis. Image source: Wikipedia.

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.

Leukotriene receptors mnemonic

Leukotriene
B4
BLT 1, 2 receptors

Leukotriene
C4, D4, E4
CysLT 1, 2 receptors

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:
Expression of functional leukotriene B(4) receptors on human airway smooth muscle cells.
Watanabe S, Yamasaki A, Hashimoto K, Shigeoka Y, Chikumi H, Hasegawa Y, Sumikawa T, Takata M, Okazaki R, Watanabe M, Yokogawa T, Yamamura M, Hayabuchi T, Gerthoffer WT, Halayko AJ, Shimizu E. J Allergy Clin Immunol. 2009 May 26. [Epub ahead of print]
Mast Cells and Basophils
Mnemonics: Mast Cells and Basophils