Genetic background determines mouse strain differences in inflammatory angiogenesis

Abstract

Inflammation and angiogenesis are key components of fibrovascular tissue growth, a biological event underlying both physiological (wound healing) and pathological conditions (tumor development, chronic inflammation). We investigated these components in three frequently used mouse strains (Swiss, Balb/c and C57BL/6J) to verify the influence of genetic background on the kinetics of inflammatory cell recruitment/activation, neovascularization, extracellular matrix deposition, and cytokine production in polyether-polyurethane sponge implanted subcutaneously in male mice of these strains. The kinetics of neutrophil recruitment/activation as assessed by myeloperoxidase (MPO) activity was 2- and 3-fold higher in Balb/c implants at day 1 compared with Swiss and C57BL/6J implants, respectively. Macrophage accumulation/activation as NAG (n-acetyl β-glucosaminidase) activity was higher in Swiss implants. The levels the monocyte chemoattractant protein 1 (CCL2(MCP-1)) peaked at day 10 in the three types of implants but was produced more by C57BL/6J mice. Angiogenesis (hemoglobin, vascular endothelial growth factor-VEGF, and number of vessels) differed among the strains. Swiss implants had the highest hemoglobin content but the lowest VEGF levels. In contrast, Balb/c implants had higher VEGF levels but lower hemoglobin. Collagen deposition and transforming growth factor β-1; TGFβ-1 levels also varied among the groups. Swiss and Balb/c implants had progressive increase in TGFβ-1 from 4 to 14 days, while C57BL/6J implants achieved the peak at day 10 and fell at day 14. These findings emphasize the major contribution of genetic background in the temporal pattern and intensity of inflammatory angiogenesis components that may have functional consequences in physiological and pathological conditions where these processes co-exist.

Trypanosoma cruzi antigens induce inflammatory angiogenesis in a mouse subcutaneous sponge model

“…The subcutaneous sponge model, a well-established model for angiogenesis investigation was chosen due to the possibility to study the role of antigens of T. cruzi instead of live parasites. Studies involving the sponge model showed that this model presents an initial phase (1-3 days) with the predominance of neutrophils, an intermediate stage (4-8 days) with the predominance of macrophages and a final stage (8-15 days) where there is reduction of inflammatory cells with the predominance of blood vessels and collagen in the matrix of the sponge (Andrade et al, 1987;Barcelos et al, 2005;Teixeira et al, 2005;Marques et al, 2011). This is the first study involving administration of total antigen of the Y strain of T. cruzi and as demonstrated in Fig.…”

“…In parallel, the infiltration of mononuclear cells into the implants was quantified by measuring the levels of the lysosomal enzyme Nacetyl-β-D-glucosaminidase (NAG) which is present in high levels in activated monocytes/macrophages (Barcelos et al, 2004;Marques et al, 2011). Part of the pellet that remained after the hemoglobin measurement was kept for this assay.…”

PLGA nanofibers improves the antitumoral effect of daunorubicin

“…The extent of the vascularization of the sponge was assessed in terms of the amount of Hb that was detected in the tissue using the aforementioned Drabkin method [27][28][29][30]. The Hb concentration in the samples was determined spectrophotometrically by measuring the absorbance at 540 nm.…”

“…The Hb content in the implant was expressed as g Hb per mg wet weight. The cytokine VEGF was measured following the protocol described in previously published studies [28,30]. The neutrophils in the sponge were measured by assaying the MPO activity, as has been described in the literature [27][28][29][30].…”

“…The results were expressed as the change in OD/mg wet weight. The infiltration of mononuclear cells into the sponge was quantified by monitoring the levels of the lysosomal enzyme NAG, which was present in high levels in the activated macrophages, by measuring the absorption at 400 nm [27][28][29][30].…”