immunology of infectious and parasitic diseases - XXXVII Congress ...

PURINERGIC RECEPTOR P2Y12 ACTIVATION IN SCHISTOSOMAL HOST
RESPONSE
VALDIRENE S. MUNIZ 1 ; RENATA B. REIS 1 ; HILTON A. MATA-SANTOS 2 ;
ALEXANDRE S. PYRRHO 2 ; PETER F. WELLER 3 ; RODRIGO T. FIGUEIREDO 4
AND JOSIANE S. NEVES 1
1 Institute of Biomedical Sciences, 2 Faculty of Pharmacy, Federal University of Rio de
Janeiro, Rio de Janeiro, RJ, Brazil, 3 Division of Allergy and Inflammation, Harvard
Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA, 4 Institute
of Biomedical Sciences/Unit of Xerem.
Introduction: Identification of new target molecules through which eosinophils
activate and secrete their stored proteins may be highly significant for our
understanding about the pathophysiology of host immune responses to parasites
and allergic inflammation, as well as reveal new therapeutic targets for the control of
the eosinophilic disorders. We have recently reported the expression of the
purinergic P2Y12 receptor (P2Y12R) in human eosinophils (JACI 125:477-482,
2010), however, their involvement in eosinophilic inflammatory conditions in vivo,
particularly in host response to parasites is still unknown.
In this work we investigated the role of the purinergic P2Y12R in the eosinophilic
inflammatory response induced by Shistosoma mansoni (S. mansoni) infection.
Methods and Results: C57Bl/6 mice were infected with 50 cercariae of the BH
strain of S. mansoni by the cutaneous route (protocol licence CEUA/UFRJ
DFBCICB043). The animals were treated with a P2Y12R antagonist, clopidogrel
(500μg/mL), via the drinking water three days before and throughout the infection
period (55 days). Histopathological and biochemical analyses were performed in the
liver to evaluate the areas of inflammatory granulomatous infiltrate and collagen
deposition. The P2Y12R blockage reduced the hepatic inflammatory infiltrate around
the granuloma – not treated: 5.47 ± 1.8 versus treated 4.2 ± 1.6 (x10 4
μm 2 /granuloma), means ± EPM, N=5 - as well as liver collagen deposition – not
treated: 880 ± 7 versus treated 690 ± 6 (μg hydroxyproline/g liver), means ± EPM,
N=5 - without altering the parasite oviposition. Furthermore, the P2Y12R inhibition
promoted blood eosinophilia (2-fold increase, N=5), whereas decreased the
eosinophil count in the bone marrow (60% reduction, N=5) after blood smears and
cytospin analyses, respectively.
Conclusion: Our results indicate an important role of the P2Y12R in the modulation
of the host inflammatory response caused by S. mansoni infection. Our studies
might enhance understanding of the importance of eosinophil activation and
migration to parasite infected sites.
Financial support : FAPERJ and CNPq.