Ablation of TrkA function in the immune system causes B cell abnormalities

Coppola, Vincenzo; Barrick, Colleen; Southon, Eileen; Celeste, Arkady; Wang, Kathryn; Chen, Bei; Haddad, El-Bdaoui; Yin, Jiehui Kevin; Nussenzweig, André; Subramaniam, Arun; Tessarollo, Lino

doi:10.1242/dev.01383

Cited by 62 publications

(52 citation statements)

References 52 publications

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“…1D). These ''floxed'' AM mice were crossed with transgenic mice expressing Cre under either an ubiquitous promoter or the tubulin T␣-1 promoter (18). This second promoter induces expression of Cre protein in neurons of the CNS during neurogenesis.…”

Section: Resultsmentioning

confidence: 99%

“…The resulting animals were crossed until a homozygous colony where the adm gene was surrounded by loxP sequences (floxed) was created. The floxed adm mice were crossed with animals expressing Cre under either a ubiquitous promoter or the tubulin T␣-1 promoter (18). Cre expressing mice were generated in a mixed C57BL/6J-C3H/ HeJ background and backcrossed 5 generations in a C57BL/6J background before being used for experimental crosses.…”

Section: Methodsmentioning

confidence: 99%

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Lack of adrenomedullin in the mouse brain results in behavioral changes, anxiety, and lower survival under stress conditions

Fernández

Serrano²,

Tessarollo³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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The adrenomedullin (AM) gene, adm, is widely expressed in the central nervous system (CNS) and several functions have been suggested for brain AM. Until now, a formal confirmation of these actions using genetic models has been elusive since the systemic adm knockout results in embryo lethality. We have built a conditional knockout mouse model using the Cre/loxP approach. When crossed with transgenic mice expressing the Cre recombinase under the tubulin T␣-1 promoter, we obtained animals with no AM expression in the CNS but normal levels in other organs. These animals lead normal lives and do not present any gross morphological defect. Specific areas of the brain of animals lacking CNS AM contain hyperpolymerized tubulin, a consequence of AM downregulation. Behavioral analysis shows that mice with no AM in their brain have impaired motor coordination and are hyperactive and overanxious when compared to their wild-type littermates. Treatment with methylphenidate, haloperidol, and diazepam did not show differences between genotypes. Circulating levels of adrenocorticotropic hormone and corticosterone were similar in knockout and wild-type mice. Animals with no brain AM were less resistant to hypobaric hypoxia than wild-type mice, demonstrating the neuroprotective function of AM in the CNS. In conclusion, AM exerts a beneficial action in the brain by maintaining homeostasis both under normal and stress conditions. A drenomedullin (AM) is a 52-aa regulatory peptide with structural homology to calcitonin gene-related peptide (CGRP) and amylin. The adm gene is located in mouse chromosome 7 and codes for a preprohormone which, after posttranslational modifications, generates 2 biologically active peptides, AM and proadrenomedullin N-terminal 20 peptide (PAMP). Expression of these peptides is widespread and several functions have been ascribed to these molecules, including vasodilatation, bronchodilatation, hormone secretion regulation, growth modulation, angiogenesis promotion, and antimicrobial activity, among others (1). The receptor system for AM consists of a heterodimer composed of calcitonin receptor-like receptor (CLR) and receptor activity modifying protein (RAMP) type 2 or 3 (2).In the CNS, AM was initially found in the hypothalamus (3), but later on it became clear that this peptide is expressed throughout the whole brain (4). Components of the AM receptor system are also found in most areas of the brain (5), providing an anatomical basis for the implication of AM in brain physiology. Receptor autoradiography studies have shown that AM is able to bind to many areas of the brain, as well (6). Recently, a new member of the CGRP/AM peptide family, with a peptide sequence similar to AM but coded by a different gene, has been reported and named AM2 or intermedin. This peptide has similar actions and distribution in the brain to original AM (7).Several observations suggest that AM could act as a neurotransmitter or neuromodulator. For instance, direct injection of AM in the CNS induces vasoconstriction (8), an incre...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Lack of adrenomedullin in the mouse brain results in behavioral changes, anxiety, and lower survival under stress conditions

Fernández

Serrano²,

Tessarollo³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

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show abstract

“…were divided into 3 groups. Control group was untreated (n=2 for each gender); the second group was subjected to CRS for 3 cycles (n= [3][4][5]; and the third group were injected with purified mouse fibroblast OPN (n= [3][4][5]. Each mouse received 5 μg of OPN daily for 3 days before and 3 days during the CRS.…”

Section: Opn Injection In Opn-deficient Micementioning

confidence: 99%

Osteopontin: Role in immune regulation and stress responses

Wang¹,

Denhardt²

2008

Cytokine & Growth Factor Reviews

609

558

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“…Although neurotrophins are best characterized as trophic factors for neurons during development and adulthood, including regulation of synaptic plasticity and growth cone guidance (Bibel and Barde 2000, Kaplan and Miller 2000, Lu et al 2005) numerous reports have uncovered critical roles for neurotrophins and their receptors on non-neuronal cells, such as endothelial cells, smooth muscle cells, immune cells, and epithelial cells in different organs, (Nemoto et al 1998, Botchkarev et al 1999, Coppola et al 2004). Interestingly, p75 NTR is increased following vascular injury, and its expression correlates both temporally and spatially with apoptosis of neointimal smooth muscle cells (Kraemer 2002).…”

Section: Biology Of Neurotrophins and Their Receptorsmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor: A Newly Described Mediator of Angiogenesis

Kermani

Hempstead

2007

Trends in Cardiovascular Medicine

282

193

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Recent studies indicate that, in addition to its neuropoietic actions, brain derived neurotrophic factor (BDNF) promotes endothelial cell survival and induces neoangiogenesis in ischemic tissues. Unlike many vascular growth factors that act on many vascular beds, BDNF activity is relatively restricted to central arteries and cardiac skeletal muscle, skin and vasculature. Studies of newly described biological mediators that act on large vessel and microvascular beds in these organs will help us to better understand organ-specific vascular development as well as to develop novel therapeutic strategies to improve the condition of patients with cardiac and peripheral vascular disease. In this review we summarize dual pro-angiogenic actions of BDNF, which through local activation of TrkB receptor expressed on a sub-population of endothelial cells (ECs) and additionally by recruitment of bone marrow-derived cells, contribute to neoangiogenesis. Importance of endothelial cells in angiogenesis.The development of a mature vascular bed is a complex and dynamic process, characterized by the coordinated proliferation and recruitment of endothelial and smooth muscle cells and subsequent patterning into capillaries, arteries and veins. It is controlled by locally produced growth factors, adhesion molecules and proteinases (Carmeliet 2000) that establish the primary vascular plexus consisting of endothelial cells. Subsequently, accessory cells such as pericytes and smooth muscle cells are recruited to sculpt the vasculature, by pruning and remodeling. During adulthood, the maintenance of blood vessels is further promoted by a combination of growth factors, cell:matrix interactions and shear stress forces. The molecular mechanisms that are utilized during development to sculpt the immature vascular bed may be utilized during the adaptive neovascularization of the heart that occurs as a consequence of cardiac ischemia.Endothelial cells, comprising the inner layer of cells of the vasculature, are the main regulators of vascular homeostasis. They play important roles in the physiology and maintenance of vascular integrity and tone, as well as in pathological situations such as inflammation and tumor angiogenesis. Although endothelial cells exhibit many common morphological characteristics, they display significant heterogeneity in different organs, to promote organ-specific functions (Garlanda and Dejana 1997). While coronary arteries nourish the myocardium, the highly specialized endothelial cells in the bone marrow sinusoids are intimately involved in the homing of hematopoietic progenitors and play an important role in maturation, proliferation and trafficking of those cells to the blood circulation. These characteristics may be endowed by organ-specific growth factors secreted by parenchymal cells in a paracrine manner.The healthy endothelium is both anti-coagulant and anti-thrombotic, by expressing or secreting numerous proteins that regulate blood coagulation and platelet activation (Robson et al.

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Ablation of TrkA function in the immune system causes B cell abnormalities

Cited by 62 publications

References 52 publications

Lack of adrenomedullin in the mouse brain results in behavioral changes, anxiety, and lower survival under stress conditions

Lack of adrenomedullin in the mouse brain results in behavioral changes, anxiety, and lower survival under stress conditions

Osteopontin: Role in immune regulation and stress responses

Brain-Derived Neurotrophic Factor: A Newly Described Mediator of Angiogenesis

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