Neutrophil Sphingosine 1-Phosphate and Lysophosphatidic Acid Receptors in Pneumonia

• Published in: American journal of respiratory cell and molecular biology Vol. 34; no. 2; pp. 233 - 241
• Main Authors: Rahaman, Matiur, Costello, Richard W, Belmonte, Kristen E, Gendy, Samir S, Walsh, Marie-Therese
• Format: Journal Article
• Language: English
• Published: United States Am Thoracic Soc 01-02-2006; American Thoracic Society
• Subjects: Adult; Aged; Aged, 80 and over; Case-Control Studies; Chemotaxis - drug effects; Dimerization; Female; Gene Expression; Humans; Lysophospholipids - metabolism; Lysophospholipids - pharmacology; Male; Middle Aged; Neutrophils - drug effects; Neutrophils - metabolism; Neutrophils - pathology; Pneumonia - metabolism; Pneumonia - pathology; Protein Isoforms; Receptors, Interleukin-8A - genetics; Receptors, Interleukin-8A - metabolism; Receptors, Lysophosphatidic Acid - genetics; Receptors, Lysophosphatidic Acid - metabolism; Receptors, Lysophospholipid - metabolism; Reference Values; Sphingosine - analogs & derivatives; Sphingosine - metabolism; Sphingosine - pharmacology
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/rcmb.2005-0126OC

The phospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via transmembrane receptors S1P 1-5 and LPA 1-3, respectively. Both have been implicated in inflammatory responses. S1P and LPA receptor profiles on neutrophils of patients with pneumonia compared with healthy subjects were determined by PCR and Western blotting. Chemotaxis studies were performed to assess functional differences. S1P or LPA receptors were immunoprecipitated from neutrophils to assess receptor heterodimerization with CXCR1, an IL-8 receptor, by Western blotting. Receptors S1P 1, 4, and 5 and LPA 2 were expressed on neutrophils from both subject groups, but S1P 3 and LPA 1 receptor expression was mainly confined to neutrophils of patients with pneumonia. Chemotaxis of neutrophils from patients with pneumonia compared with control subjects was significantly increased in response to S1P and LPA. Pretreatment with S1P or LPA reduced IL-8-induced neutrophil chemotaxis and transcriptional expression of the CXCR1 receptor. Receptors S1P 3 and 4 and LPA 1 formed constitutive heterodimers with CXCR1. LPA treatment reduced the amount of LPA 1/CXCR1 heterodimer. Therefore, profiles of S1P and LPA receptors differ between neutrophils of patients with pneumonia and control subjects, with consequences for neutrophil function.