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

Abstract

Abstract. 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 mg / 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 Rhoassociated 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.

Protein Kinase Cδ Mediates Lysophosphatidic Acid-induced NF-κB Activation and Interleukin-8 Secretion in Human Bronchial Epithelial Cells

“…These results suggest that accumulation of LPA in the airway induces accumulation of neutrophils and other inflammatory cells at local sites of injury and inflammation. LPA (1-10 g/ml) instilled into guinea pig airways substantially increased eosinophils and neutrophils in BAL fluid after 4 h of inhalation, which was blocked by Y-27632, an inhibitor of Rho-associated protein kinase (23). The in vivo studies in murine and guinea pig models of airway 2 E. Berdyshev, S. Georas, A. J. Morris, R. Cummings, W. Hubbard, M. Liu, and V. Natarajan, manuscript in preparation.…”

“…LPA is a potent bioactive lipid that mediates several cellular responses such as proliferation, differentiation, suppression of apoptosis, tumor metastasis, and cytoskeletal reorganization (15,(21)(22)(23)(24)(25)(26)(27)(28). LPA mediates the broad range of cellular responses through the G-protein-coupled receptors LPA 1 /Edg-2, LPA 2 /Edg-4, and LPA 3 /Edg-7 (19).…”

“…Studies in our laboratory have revealed that S1P stimulates significant production and secretion of IL-8 in a human bronchial epithelial cell line (BEAS-2B) (21) and that LPA is capable of transactivating platelet-derived growth factor receptor-␤ in HBEpCs (20). In guinea pigs, administration of exogenous LPA into the airway enhances the response to acetylcholine (22) and infiltration of neutrophils (23). Other reports have shown that LPA induces airway smooth muscle contractility (24), proliferation (25), and transcription factor activation (26).…”

Distinct roles of ROCK1 and ROCK2 during development of porcine preimplantation embryos

“…ROCK activity can be induced in mammalian cells by lysophosphatidic acid (LPA; Hashimoto et al 2003). Addition of LPA has been reported to improve the development of mouse preimplantation embryos (Kobayashi et al 1994).…”

Lysophosphatidic Acid Enhances Pulmonary Epithelial Barrier Integrity and Protects Endotoxin-induced Epithelial Barrier Disruption and Lung Injury

“…Extracellular activities of LPA include cell proliferation, motility, and cell survival (27)(28)(29)(30). LPA exhibits a wide range of effects on differing cell types, including pulmonary epithelial, smooth muscle, fibroblasts, and T cells (31)(32)(33)(34)(35). LPA augments migration and cytokine synthesis in lymphocytes and induces chemotaxis of Jurkat T cells through Matrigel membranes (34).…”