Lysophosphatidic Acid Enhances In Vivo Infiltration and Activation of Guinea Pig Eosinophils and Neutrophils via a Rho/Rho-Associated Protein Kinase-Mediated Pathway

• Published in: Journal of Pharmacological Sciences Vol. 91; no. 1; pp. 8 - 14
• Main Authors: Hashimoto, Terumasa, Yamashita, Miyuki, Ohata, Hisayuki, Momose, Kazutaka
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Pharmacological Society 2003; Elsevier
• Subjects: Amides - pharmacology; Animals; Bronchoalveolar Lavage Fluid - cytology; Enzyme Inhibitors - pharmacology; Eosinophils - drug effects; Eosinophils - metabolism; Guinea Pigs; inflammatory cell; Intracellular Signaling Peptides and Proteins; lysophosphatidic acid; Lysophospholipids - pharmacology; Male; Neutrophils - drug effects; Neutrophils - metabolism; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - physiology; Pyridines - pharmacology; rho-Associated Kinases; Rho-associated protein kinase; superoxide production; Superoxides - metabolism
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.91.8

Lysophosphatidic acid (LPA) has been shown to be a chemoattractant in in vitro studies. The present study was carried out to determine whether LPA enhances infiltration of inflammatory cells in in vivo studies with guinea pigs. LPA (1 – 10 μg/ml), when by guinea pigs for 5 min, substantially increased the numbers of eosinophils and neutrophils in the bronchoalveolar lavege fluid (BALF), which was recovered at over 4 h after the inhalation of LPA. Infiltration in BALF was significantly inhibited by inhalation of Y-27632, an inhibitor of Rho-associated protein kinase (ROCK). LPA also increased superoxide production of eosinophils and neutrophils. In contrast, Y-27632 inhibited superoxide production. These findings suggest that LPA may contribute to infiltration and activation of inflammatory cells in bronchial asthma; furthermore, the Rho/ROCK-mediated pathway may be involved.