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Cellular renewal and improvement of local cell effector activity in peritoneal cavity in response to infectious stimuli.

ABSTRACT: The peritoneal cavity (PerC) is a singular compartment where many cell populations reside and interact. Despite the widely adopted experimental approach of intraperitoneal (i.p.) inoculation, little is known about the behavior of the different cell populations within the PerC. To evaluate the dynamics of peritoneal macrophage (MØ) subsets, namely small peritoneal MØ (SPM) and large peritoneal MØ (LPM), in response to infectious stimuli, C57BL/6 mice were injected i.p. with zymosan or Trypanosoma cruzi. These conditions resulted in the marked modification of the PerC myelo-monocytic compartment characterized by the disappearance of LPM and the accumulation of SPM and monocytes. In parallel, adherent cells isolated from stimulated PerC displayed reduced staining for ?-galactosidase, a biomarker for senescence. Further, the adherent cells showed increased nitric oxide (NO) and higher frequency of IL-12-producing cells in response to subsequent LPS and IFN-? stimulation. Among myelo-monocytic cells, SPM rather than LPM or monocytes, appear to be the central effectors of the activated PerC; they display higher phagocytic activity and are the main source of IL-12. Thus, our data provide a first demonstration of the consequences of the dynamics between peritoneal MØ subpopulations by showing that substitution of LPM by a robust SPM and monocytes in response to infectious stimuli greatly improves PerC effector activity.

SUBMITTER: Cassado Ados A

PROVIDER: S-EPMC3142143 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Cellular renewal and improvement of local cell effector activity in peritoneal cavity in response to infectious stimuli.

Cassado Alexandra dos Anjos Ados A de Albuquerque José Antônio Tavares JA Sardinha Luiz Roberto LR Buzzo Carina de Lima Cde L Faustino Lucas L Nascimento Rogério R Ghosn Eliver Eid Bou EE Lima Maria Regina D'Império MR Alvarez Jose Maria Mosig JM Bortoluci Karina Ramalho KR

PloS one 20110722 7

The peritoneal cavity (PerC) is a singular compartment where many cell populations reside and interact. Despite the widely adopted experimental approach of intraperitoneal (i.p.) inoculation, little is known about the behavior of the different cell populations within the PerC. To evaluate the dynamics of peritoneal macrophage (MØ) subsets, namely small peritoneal MØ (SPM) and large peritoneal MØ (LPM), in response to infectious stimuli, C57BL/6 mice were injected i.p. with zymosan or Trypanosoma ...[more]

PMID: 21799778

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Project description:IntroductionAbdominal obesity increases the risk of developing ovarian cancer but the molecular mechanisms of how obesity supports ovarian cancer development remain unknown. Here we investigated the impact of obesity on the immune cell and gene expression profiles of distinct abdominal tissues, focusing on the peritoneal serous fluid (PSF) and the omental fat band (OFB) as critical determinants for the dissemination of ovarian metastases and early metastatic events within the peritoneal cavity.MethodsFemale C57BL/6 mice were fed a low-fat (LFD) or a high-fat diet (HFD) for 12 weeks until the body weights in the HFD group were significantly higher and the mice displayed an impaired glucose tolerance. Then the mice were injected with the murine ovarian cancer cells (MOSE-LTICv) while remaining on their diets. After 21 days, the mice were sacrificed, tumor burden was evaluated and tissues were harvested. The immune cell composition of abdominal tissues and changes in gene expression in the PSF and OFB were evaluated by flow cytometry and qPCR RT2-profiler PCR arrays and confirmed by qRT-PCR, respectively. Other peritoneal adipose tissues including parametrial and retroperitoneal white adipose tissues as well as blood were also investigated.ResultsWhile limited effects were observed in the other peritoneal adipose tissues, feeding mice the HFD led to distinct changes in the immune cell composition in the PSF and the OFB: a depletion of B cells but an increase in myeloid-derived suppressor cells (MDSC) and mono/granulocytes, generating pro-inflammatory environments with increased expression of cyto- and chemokines, and genes supporting adhesion, survival, and growth, as well as suppression of apoptosis. This was associated with a higher peritoneal tumor burden compared to mice fed a LFD. Changes in cellular and genetic profiles were often exacerbated by the HFD. There was a large overlap in genes that were modulated by both the HFD and the cancer cells, suggesting that this 'genetic fingerprint' is important for ovarian metastases to the OFB.DiscussionIn accordance with the 'seed and soil' theory, our studies show that obesity contributes to the generation of a pro-inflammatory peritoneal environment that supports the survival of disseminating ovarian cancer cells in the PSF and the OFB and enhances the early metastatic adhesion events in the OFB through an increase in extracellular matrix proteins and modulators such as fibronectin 1 and collagen I expression as well as in genes supporting growth and invasion such as Tenacin C. The identified genes could potentially be used as targets for prevention strategies to lower the ovarian cancer risk in women with obesity.

Project description:BackgroundWe tested the hypothesis that the mouse peritoneum can function like a bioreactor to generate directed bio-engineered tissues such as those used for bypass grafting. Additionally, we reasoned that the mouse animal model would allow us to elucidate the underlying cellular and molecular mechanisms that are responsible for the generation of tissue in peritoneal cavity.MethodsPlastic tubes (two tubes/mouse) were implanted into the peritoneal cavity of three strains of mice (C57BL/6, BALB/c, and MRL). The tubes were harvested, tissue capsule surrounding the tubes was removed, and analyzed by immunostaining (five capsules/five mice/strain) and microarray (three capsules/three mice/strain). In addition, the tissue capsules that were harvested from MRL mice (n = 21) were grafted into abdominal aorta of the same mice as autografts. The patency of all grafts was monitored by micro-ultrasound, and their functionality was assessed by laser Doppler imaging of blood flow in femoral arteries. Venous (n = 13) and arterial isografts (n = 11) were used as positive controls. In a negative control group (five mice/strain), the abdominal aorta was occluded by double ligation with 9-0 silk.ResultsThe implanted plastic tubes required at least 8 weeks of incubation in the peritoneum of the three strains of mice in order to generate useful grafts. No vascular cells were found in the tissue capsules. Microarray analysis of tissue capsules revealed that the capsular cells express a gene expression program that is vastly shared among the three strains of mice, and the cells exhibit a high degree of plasticity. The micro-ultrasound analysis of the grafts showed that 62% of autografts remained patent compared with 77% of venous isografts and 91% of arterial isografts. The laser Doppler imaging analysis showed that blood flow dropped by 40% and 35% in the autografts and vein isografts, respectively, 1 day after surgery. The flow, however, rebounded to the level of arterial isografts 1 month post-surgery and remained unchanged among all grafts for the next 4 months. Immunostaining of the autografts showed a thick vessel wall with endothelial cells that lined the lumen and smooth muscle cells that constituted the graft wall.ConclusionThe mouse peritoneal cavity of mice has the ability to function like a bioreactor to generate bio-engineered tissues. The tissue capsules harvested from peritoneal cavity of a mouse are composed of nonvascular cells that display phenotype of progenitor cells. After grafting, however, the capsule autografts become arterialized and remained patent for at least 4 months after surgery, similar to venous or arterial isografts.

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Cellular renewal and improvement of local cell effector activity in peritoneal cavity in response to infectious stimuli.

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Cellular renewal and improvement of local cell effector activity in peritoneal cavity in response to infectious stimuli.

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