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Vanderslice, Peter; Munsch, Christy L.; Rachal, Eugene; Erichsen, David; Sughrue, Kay M.; Truong, Ann N.; Wygant, James N.; McIntyre, Bradley W.; Eskin, Suzanne G.; Tilton, Ronald G.; Polverini, Peter J.

doi:10.1023/a:1009296700991

Cited by 36 publications

(14 citation statements)

References 44 publications

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“…18,54–56 Ablation of macrophages has been shown to reduce angiogenesis during wound healing, 57 but there are no in vivo studies on the effect of macrophage depletion on the proangiogenic activity of TNFα. To evaluate the role of macrophages in TNFα-induced angiogenesis, we pretreated aortic rings with liposomal clodronate which selectively kills phagocytic cells.…”

Section: Discussionmentioning

confidence: 99%

Macrophage-Derived Tumor Necrosis Factor-α Is an Early Component of the Molecular Cascade Leading to Angiogenesis in Response to Aortic Injury

Ligresti

Aplin

Zorzi

et al. 2011

ATVB

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Objective To define the role of TNFα in the cascade of gene activation that regulates aortic angiogenesis in response to injury. Methods and Results Angiogenesis was studied by culturing rat or mouse aortic rings in collagen gels. Gene expression was evaluated by qRT-PCR, microarray analysis, immunocytochemistry and ELISA. TNFα gene disruption and recombinant TNFα or blocking antibodies against VEGF or TNFRs were used to investigate TNFα-mediated angiogenic mechanisms. Resident aortic macrophages were depleted with liposomal clodronate. Angiogenesis was preceded by overexpression of TNFα and TNFα-inducible genes. Studies with isolated cells showed that macrophages were the main source of TNFα. Angiogenesis, VEGF production, and macrophage outgrowth were impaired by TNFα gene disruption and promoted by exogenous TNFα. Antibody-mediated inhibition of TNFR1 significantly inhibited angiogenesis. The proangiogenic effect of TNFα was suppressed by blocking VEGF or by ablating aortic macrophages. Exogenous TNFα, however, maintained a limited proangiogenic capacity in the absence of macrophages and macrophage-mediated VEGF production. Conclusions Overexpression of TNFα is required for optimal VEGF production and angiogenesis in response to injury. This TNFα/VEGF-mediated angiogenic pathway requires macrophages. The residual capacity of TNFα to stimulate angiogenesis in macrophage-depleted aortic cultures implicates the existence of a VEGF-independent alternate pathway of TNFα-induced angiogenesis.

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Section: Discussionmentioning

confidence: 99%

Macrophage-Derived Tumor Necrosis Factor-α Is an Early Component of the Molecular Cascade Leading to Angiogenesis in Response to Aortic Injury

Ligresti

Aplin

Zorzi

et al. 2011

ATVB

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“…Interestingly, the angiogenic defect we reported in the Rac2 knockout mouse model [1] seems to reflect a specific defect in postnatal angiogenesis in that these mice have no developmental angiogenic/vasculogenic defect. These findings suggest an interesting hypothesis ; that Rac2 has evolved in macrophages to represent a novel mechanism by which certain growth factors and the provisional integrins, α 4 β 1 and α v β 3 , regulate the postnatal adaptive stromal angiogenic/wound healing response [14], [15], [16], [17].…”

Section: Introductionmentioning

confidence: 95%

Rac2 Controls Tumor Growth, Metastasis and M1-M2 Macrophage Differentiation In Vivo

et al. 2014

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Although it is well-established that the macrophage M1 to M2 transition plays a role in tumor progression, the molecular basis for this process remains incompletely understood. Herein, we demonstrate that the small GTPase, Rac2 controls macrophage M1 to M2 differentiation and the metastatic phenotype in vivo. Using a genetic approach, combined with syngeneic and orthotopic tumor models we demonstrate that Rac2-/- mice display a marked defect in tumor growth, angiogenesis and metastasis. Microarray, RT-PCR and metabolomic analysis on bone marrow derived macrophages isolated from the Rac2-/- mice identify an important role for Rac2 in M2 macrophage differentiation. Furthermore, we define a novel molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin and MCSF receptor lead to the activation of Rac2 and potentially regulate macrophage M2 differentiation. Collectively, our findings demonstrate a macrophage autonomous process by which the Rac2 GTPase is activated downstream of the α4β1 integrin and the MCSF receptor to control tumor growth, metastasis and macrophage differentiation into the M2 phenotype. Finally, using gene expression and metabolomic data from our Rac2-/- model, and information related to M1-M2 macrophage differentiation curated from the literature we executed a systems biologic analysis of hierarchical protein-protein interaction networks in an effort to develop an iterative interactome map which will predict additional mechanisms by which Rac2 may coordinately control macrophage M1 to M2 differentiation and metastasis.

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“…24 While there are several case studies and reports of a lack of piped water or serious water quality problems in low-income and minority communities, this issue has not been well-studied. 25 In 2010, the federal Healthy Hunger Free Kids Act required that water be made available at no cost to students in food service areas (effective for the 2011-2012 school year). Contamination of school drinking water from sources like lead pipes has been documented in a number of cities across the country, highlighting the need for additional supports for equitable potable water access.…”

Section: Introductionmentioning

confidence: 99%