Inhibitory effects of lysophosphatidic acid on human lung mast cell function

Authors and Affiliations:
Emeribe, A.U. 1, Peachell, P. 2, Kay, L. 2 1 Department of Medical Laboratory Science, University of Calabar,
Calabar-Nigeria.
2 Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield-United Kingdom

Background: Pulmonary fibrosis is an abnormal lung condition characterized by an inability to maintain regenerative processes in the lung. Although the pathological mechanisms that lead to lung fibrosis remain unclear, the activation of immune cells is almost certainly key. Recent studies in rodent cells have identified activation of the mast cell by lysophosphatidic acid (LPA) as central to the mediation of fibrosis. We hypothesized that similar processes might be operative in human mast cells so the aim of this study was to determine whether LPA activates human lung mast cells.
Methods: Mast cells were isolated and purified from human lung tissue. Expression of LPA receptor (LPAR) transcripts were evaluated using Taqman probe based qPCR. Mast cell activation was evaluated by monitoring the release of histamine using a spectrofluorometric technique. The effects of anti-IgE, and LPA on histamine release were evaluated.
Results: Data from this study revealed that LPAR1, 2 and 3 were highly expressed, LPAR5 was moderately expressed, while no expression was observed for LPAR4. LPA did not induce mediator release but unexpectedly was an effective inhibitor of anti-IgE-mediated histamine release. LPA inhibited histamine release in a concentration-dependent manner and with an EC50 of ~ 19 nM.
Conclusions and implications: This study demonstrates that human lung mast cells express LPA receptors. Moreover, the data indicate that, rather than activating mast cells, LPA was an effective inhibitor of mast cell secretion which was contrary to expectations. This suggests that targeting the relevant LPAR that mediates inhibition could be a novel mechanism to prevent unwanted mast cell activation.

Anthony Uchenna Emeribe MSc

University of Calabar

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