Ascaris suum-Derived Products Induce Human Neutrophil Activation via a G Protein-Coupled Receptor That Interacts with the Interleukin-8 Receptor Pathway
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Date
2001Author
Falcone, Franco
Rossi, Adriano G
Sharkey, Rose
Brown, Alan
Pritchard, David
Maizels, Rick
Metadata
Abstract
Infection with tissue-migrating helminths is frequently associated with intense granulocyte infiltrations.
Several host-derived factors are known to mediate granulocyte recruitment to the tissues, but less attention has
been paid to how parasite-derived products trigger this process. Parasite-derived chemotactic factors which
selectively recruit granulocytes have been described, but nothing is known about which cellular receptors
respond to these agents. The effect of products from the nematodes Ascaris suum, Toxocara canis, and Anisakis
simplex on human neutrophils were studied. We monitored four parameters of activation: chemotaxis, cell
polarization, intracellular Ca21 transients, and priming of superoxide anion production. Body fluids of A. suum
(ABF) and T. canis (TcBF) induced strong directional migration, shape change, and intracellular Ca21
transients. ABF also primed neutrophils for production of superoxide anions. Calcium mobilization in response
to A. suum-derived products was completely abrogated by pretreatment with pertussis toxin, implicating
a classical G protein-coupled receptor mechanism in the response to ABF. Moreover, pretreatment with
interleukin-8 (IL-8) completely abrogated the response to ABF, demonstrating desensitization of a common
pathway. However, ABF was unable to fully desensitize the response to IL-8, and binding to CXCR1 or CXCR2
was excluded in experiments using RBL-2H3 cells transfected with the two human IL-8 receptors. Our results
provide the first evidence for a direct interaction between a parasite-derived chemotactic factor and the host’s
chemotactic network, via a novel G protein-coupled receptor which interacts with the IL-8 receptor pathway.