Proangiogenic Tie2+ Macrophages Infiltrate Human and Murine Endometriotic Lesions and Dictate Their Growth in a Mouse Model of the Disease

Capobianco, Annalisa; Monno, Antonella; Cottone, Lucia; Venneri, Mary Anna; Biziato, Daniela; Puppo, Francesca; Ferrari, Stefano; Palma, Michele De; Manfredi, Angelo A.; Rovere‐Querini, Patrizia

doi:10.1016/j.ajpath.2011.07.029

Cited by 99 publications

(83 citation statements)

References 56 publications

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“…Our results suggest that macrophages, a key element in muscle regeneration (8,12,13,16,60,61) known to deliver antiapoptotic and survival signals in other tissues (90)(91)(92)(93)(94)(95)(96), orchestrate the survival and eventually the differentiation of transplanted mesoangioblasts. This suggests that selective modulation of the function of endogenous macrophages could represent an additional strategy to increase the efficacy of stem cell transplantation.…”

Section: Discussionmentioning

confidence: 93%

Transplanted Mesoangioblasts Require Macrophage IL-10 for Survival in a Mouse Model of Muscle Injury

Bosurgi

Corna

Vezzoli

et al. 2012

The Journal of Immunology

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The aim of this study was to verify whether macrophages influence the fate of transplanted mesoangioblasts—vessel-associated myogenic precursors—in a model of sterile toxin-induced skeletal muscle injury. We have observed that in the absence of macrophages, transplanted mesoangioblasts do not yield novel fibers. Macrophages retrieved from skeletal muscles at various times after injury display features that resemble those of immunoregulatory macrophages. Indeed, they secrete IL-10 and express CD206 and CD163 membrane receptors and high amounts of arginase I. We have reconstituted the muscle-associated macrophage population by injecting polarized macrophages before mesoangioblast injection: alternatively activated, immunoregulatory macrophages only support mesoangioblast survival and function. This action depends on the secretion of IL-10 in the tissue. Our results reveal an unanticipated role for tissue macrophages in mesoangioblast function. Consequently, the treatment of muscle disorders with mesoangioblasts should take into consideration coexisting inflammatory pathways, whose activation may prove crucial for its success.

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Section: Discussionmentioning

confidence: 93%

Transplanted Mesoangioblasts Require Macrophage IL-10 for Survival in a Mouse Model of Muscle Injury

Bosurgi

Corna

Vezzoli

et al. 2012

The Journal of Immunology

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“…To mimic human carcinomatosis, which depends on the dissemination in the peritoneal cavity of neoplastic cells derived from tumors of abdominal organs, we injected increasing numbers of MC-38 carcinoma cells, a line which has been derived from a primary poorly immunogenic neoplasm, 15 in the peritoneal cavity of syngeneic immunocompetent mice. As little as 205 thousand cells were sufficient to elicit experimental carcinomatosis in all injected mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…This is in agreement with what has been previously shown in human and in experimental model of peritoneal disease, including ovarian cancer 1920,21 and endometriosis. 15,22 In the latter condition, macrophages deliver signals that contribute to the attraction of neo-vessels, possibly facilitating the survival of ectopic endometrial cells in the peritoneal cavity, a relatively hypoxic environment. 23 A license from macrophages could as well be required when cancer cells derived from abdominal organs adhere to the serosal lining.…”

Section: Discussionmentioning

confidence: 99%

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Leukocytes recruited by tumor-derived HMGB1 sustain peritoneal carcinomatosis

et al. 2016

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The factors that determine whether disseminated transformed cells in vivo yield neoplastic lesions have only been partially identified. We established an ad hoc model of peritoneal carcinomatosis by injecting colon carcinoma cells in mice. Tumor cells recruit inflammatory leukocytes, mostly macrophages, and generate neoplastic peritoneal lesions. Phagocyte depletion via clodronate treatment reduces neoplastic growth. Colon carcinoma cells release a prototypic damage-associated molecular pattern (DAMP)/alarmin, High Mobility Group Box1 (HMGB1), which attracts leukocytes. Exogenous HMGB1 accelerates leukocyte recruitment, macrophage infiltration, tumor growth and vascularization. Lentiviral-based HMGB1 knockdown or pharmacological interference with its extracellular impair macrophage recruitment and tumor growth. Our findings provide a preclinical proof of principle that strategies based on preventing HMGB1-driven recruitment of leukocytes could be used for treating peritoneal carcinomatosis.

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“…6 Studies investigating macrophage activation and recruitment have revealed that endometriosis-associated macrophages exhibit a phenotype consistent with the alternative end of the macrophage activation spectrum. 7,8 In a mouse model of endometriosis that included cell transfer of polarized macrophages, Bacci et al 7 reported that mice injected with proinflammatory macrophages [macrophage (interferon g)] developed microscopic lesions, but those injected with alternatively activated macrophages [macrophage (IL-4)] developed larger lesions with a well-developed vasculature. Our studies in a mouse model of endometriosis have revealed that macrophages resident in peritoneal lesions can originate from both the peritoneum and the endometrium.…”

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confidence: 99%

Estradiol Is a Critical Mediator of Macrophage-Nerve Cross Talk in Peritoneal Endometriosis

Greaves

Temp

Esnal-Zufiurre

et al. 2015

The American Journal of Pathology

131

121

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Endometriosis occurs in approximately 10% of women and is associated with persistent pelvic pain. It is defined by the presence of endometrial tissue (lesions) outside the uterus, most commonly on the peritoneum. Peripheral neuroinflammation, a process characterized by the infiltration of nerve fibers and macrophages into lesions, plays a pivotal role in endometriosis-associated pain. Our objective was to determine the role of estradiol (E2) in regulating the interaction between macrophages and nerves in peritoneal endometriosis. By using human tissues and a mouse model of endometriosis, we demonstrate that macrophages in lesions recovered from women and mice are immunopositive for estrogen receptor b, with up to 20% being estrogen receptor a positive. In mice, treatment with E2 increased the number of macrophages in lesions as well as concentrations of mRNAs encoded by Csf1, Nt3, and the tyrosine kinase neurotrophin receptor, TrkB. By using in vitro models, we determined that the treatment of rat dorsal root ganglia neurons with E2 increased mRNA concentrations of the chemokine C-C motif ligand 2 that stimulated migration of colony-stimulating factor 1edifferentiated macrophages. Conversely, incubation of colony-stimulating factor 1 macrophages with E2 increased concentrations of brainderived neurotrophic factor and neurotrophin 3, which stimulated neurite outgrowth from ganglia explants. In summary, we demonstrate a key role for E2 in stimulating macrophage-nerve interactions, providing novel evidence that endometriosis is an estrogen-dependent neuroinflammatory disorder. Endometriosis affects 10% of reproductive age women and is associated with persistent pelvic pain. 1 It is defined by the presence of endometrial-like tissue (lesions) found outside the uterus, most commonly on the peritoneum. The mechanisms underlying endometriosis-associated pain are poorly understood, but it has been postulated that estrogen-dependent neuroinflammation may be involved. 2 Notably, the presence of endometrial tissue fragments on the peritoneum elicits an immune response, including recruitment of macrophages, 3 blood vessels, and nerve fibers into the resultant lesions. 4,5 Within the lesions, CD68 þ macrophages have been detected in close association with nerve fibers. 6 Studies investigating macrophage activation and recruitment have revealed that endometriosis-associated macrophages exhibit a phenotype consistent with the alternative end of the macrophage activation spectrum. 7,8 In a mouse model of endometriosis that included cell transfer of polarized macrophages, Bacci et al 7 reported that mice injected with proinflammatory macrophages [macrophage (interferon g)] developed microscopic lesions, but those injected with alternatively activated macrophages [macrophage (IL-4)] developed larger lesions with a well-developed vasculature. Our studies in a mouse model of endometriosis have revealed that macrophages resident in peritoneal lesions can originate from both the peritoneum and the endometrium. 9

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Proangiogenic Tie2+ Macrophages Infiltrate Human and Murine Endometriotic Lesions and Dictate Their Growth in a Mouse Model of the Disease

Cited by 99 publications

References 56 publications

Transplanted Mesoangioblasts Require Macrophage IL-10 for Survival in a Mouse Model of Muscle Injury

Transplanted Mesoangioblasts Require Macrophage IL-10 for Survival in a Mouse Model of Muscle Injury

Leukocytes recruited by tumor-derived HMGB1 sustain peritoneal carcinomatosis

Estradiol Is a Critical Mediator of Macrophage-Nerve Cross Talk in Peritoneal Endometriosis

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