Plasma glutamate–modulated interaction of A2AR and mGluR5 on BMDCs aggravates traumatic brain injury–induced acute lung injury

• DOI: 10.1084/jem.20122196
• Publication Date: 2013-03-12T04:02:03Z
• Authors: Shuang-Shuang Dai; Hao Wang; Nan Yang; Jian-Hong An; Wei Li; Ya-Lei Ning; Pei-Fang Zhu; Jiang-Fan Chen; Yuan-Guo Zhou
• Keywords: Adult; Male; Mice, Knockout; 0301 basic medicine; Adenosine; Adenosine A2 Receptor Agonists; Receptor, Adenosine A2A; Receptor, Metabotropic Glutamate 5; Acute Lung Injury; Glutamic Acid; Bone Marrow Cells; Middle Aged; Receptors, Metabotropic Glutamate; Article; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Brain Injuries; Phenethylamines; Animals; Humans; Female; Protein Kinase C

The bone marrow-derived cell (BMDC)-associated inflammatory response plays a key role in the development of acute lung injury (ALI). Activation adenosine A2A receptor (A2AR) is generally considered to be antiinflammatory, inhibiting BMDC activities protect against ALI. However, present study, we found that mouse model neurogenic ALI induced by severe traumatic brain (TBI), A2AR exerted proinflammatory effect, aggravating damage. This contrast antiinflammatory effect observed oleic acid-induced (a nonneurogenic model.) Moreover, agonist CGS21680 aggravated, whereas antagonist ZM241385 attenuated, TBI-induced damage mice. Further investigation white blood cells isolated from patients or TBI models and cultured human neutrophils demonstrated elevated plasma glutamate after interaction between metabotropic 5 (mGluR5) increase phospholipase C-protein kinase C signaling, which mediated A2AR. These results are striking well-known protective indicate different therapeutic strategies should used for treatment when targeting