Mono-(2-ethylhexyl) phthalate (MEHP)-induced neutrophil and macrophage infiltration into the testicular interstitium of peripubertal rats does not exacerbate MEHP-induced germ cell apoptosis

Autor: Jorine J. L. P. Voss, Angela R. Stermer, Rashin Ghaffari, Richa Tiwary, John H. Richburg
Rok vydání: 2018
Předmět:
Zdroj: The Journal of Immunology. 200:102.5-102.5
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.200.supp.102.5
Popis: The testis is an immune-privileged organ that maintains an immune suppressive environment. We have previously shown that exposure of postnatal day (PND) 28 Fischer rats to an acute dose of the Sertoli cell toxicant MEHP leads to an accumulation of CD11b+ cells in the testicular interstitium that correlates with a robust incidence of germ cell (GC) apoptosis. Here we hypothesize that the infiltrating immune cells contribute to GC apoptosis. PND 28 Fischer rats that received an oral dose of 700 mg/kg MEHP showed a significant infiltration of both CD11bc+/CD68+/CD163− macrophages and neutrophils, which peaked at 12 hours but had reduced by 48 hours. Testicular macrophages from MEHP-treated cells showed significantly upregulated expression of Tnfa and Il6, and the Arg1/Nos2 ratio was reduced. However, small increases in anti-inflammatory genes Il10 and Tgfb1 were also observed. Depletion of circulating monocytes with clodronate liposomes prior to MEHP-treatment reduced the macrophage influx, but did not lower GC apoptosis. Additionally, depletion of neutrophils using an anti-polymorphonuclear cell antibody prevented both macrophage and neutrophil infiltration, but also did not affect germ cell apoptosis. Together, these results show that exposure to MEHP leads to a rapid and temporary influx of pro-inflammatory monocytes and neutrophils in the interstitium of the testis. However, with this dosing paradigm, these infiltrating leukocytes do not exacerbate MEHP-induced testicular GC apoptosis. Current experiments are targeted to further investigate the functional significance of these infiltrating cells in the pathogenesis of MEHP-induced testicular injury, considering both a destructive and resolving/protective role.
Databáze: OpenAIRE
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