Absence of calcium-independent phospholipase A2 β impairs platelet-activating factor production and inflammatory cell recruitment in Trypanosoma cruzi-infected endothelial cells.

Jane Mchowat,John O Marentette,John Turk,Daniel F Hoft,Janhavi Sharma,Christopher S Eickhoff

doi:10.1002/phy2.196

Jane Mchowat, John O Marentette + Show 4 more

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https://doi.org/10.1002/phy2.196

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Abstract

Both acute and chronic phases of Trypanosoma cruzi (T. cruzi) infection are characterized by tissue inflammation, mainly in the heart. A key step in the inflammatory process is the transmigration of inflammatory cells across the endothelium to underlying infected tissues. We observed increased arachidonic acid release and platelet‐activating factor (PAF) production in human coronary artery endothelial cells (HCAEC) at up to 96 h of T. cruzi infection. Arachidonic acid release is mediated by activation of the calcium‐independent phospholipase A2 (iPLA2) isoforms iPLA2β and iPLA2γ, whereas PAF production was dependent upon iPLA2β activation alone. Trypanosoma cruzi infection also resulted in increased cell surface expression of adhesion molecules. Increased adherence of inflammatory cells to T. cruzi‐infected endothelium was blocked by inhibition of endothelial cell iPLA2β or by blocking the PAF receptor on inflammatory cells. This suggests that PAF, in combination with adhesion molecules, might contribute to parasite clearing in the heart by recruiting inflammatory cells to the endothelium.

Highlights

Trypanosoma cruzi is the protozoan parasite responsible for Chagas’ disease, which is associated with significant cardiac pathology
human coronary artery endothelial cells (HCAEC) were incubated with T. cruzi for up to 96 h and independent phospholipase A2 (iPLA2) activity, arachidonic acid release, platelet-activating factor (PAF) production, and expression of cell surface adhesion molecules were measured (Fig. 1)
Trypanosoma cruzi (MOI 0.2) infection of HCAEC increased phospholipase A2 (PLA2) activity measured in the presence of 10 mmol/L ethylene glycol tetraacetic acid (EGTA) that was significant after 24 h of infection and remained increased over 96 h (Fig. 1A)

Summary

Introduction

Trypanosoma cruzi is the protozoan parasite responsible for Chagas’ disease, which is associated with significant cardiac pathology. The acute phase of Chagas’ disease may not cause symptoms, but in the chronic phase cardiac involvement occurs in 20–30% of infected individuals and may result in congestive heart failure, cardiac arrhythmias, and death (Rassi et al 2000; Bern 2011). A long asymptomatic period separating acute and chronic phases is designated the indeterminate phase and may persist for decades. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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