Nerve Growth Factor Immunoreactivity of Mast Cells in Acute Involuted Human Thymus

Marinova, Ts.; Philipov, Stanislav; Aloe, Luigi

doi:10.1007/s10753-006-9019-6

Cited by 7 publications

(7 citation statements)

References 32 publications

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“…Mast cells are also capable of producing a potent neurotrophin, nerve growth factor,32 which is an interesting feature given recent findings that, in addition to angiogenesis, neural sprouting is a prominent feature of tendinosis 5. Our cross-sectional study did not allow us to determine whether the prominence of mast cells is causally associated with the abnormal tendon vasculature and its accompanying sensory and autonomical innervation, which are strongly implicated in symptomatic tendinopathy 33 – 38.…”

Section: Discussionmentioning

confidence: 88%

Increased mast cell numbers in human patellar tendinosis: correlation with symptom duration and vascular hyperplasia

et al. 2008

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Objectives: The cellular basis of painful tendon overuse pathology (tendinosis) is poorly understood. It has been suggested that because of the close anatomical associations between mast cells and vessels in connective tissues, mast cells may mediate the development of tendon hypervascularity or oedema. Objectives: To examine the distribution of mast cells in men and women with patellar tendinopathy. Design: Case-control study. Methods: Tendinopathic tissue was collected at open debridement of the patellar tendon and a control tendon from patients undergoing intramedullary nailing of the tibia. The tendon was assessed immunohistochemically by evaluating the distribution of mast cells (AA1), and markers for T lymphocytes (CD3) and macrophages (CD68). The vessel-area fraction was quantified using computer-assisted digital image analysis. Results: The prevalence of mast cells per mm 2 (mean 3.3 (SD 3.0)) was greater in tendinosis tissue than in controls (1.1 (1.5); p = 0.036). In patients with tendinosis, mast cell density was moderately correlated with the vesselarea fraction (r 2 = 0.49) and with symptom duration (r 2 = 0.52). Conclusion: Mast-cell prevalence in patellar tendinopathy was increased and was predominantly associated with vascular hyperplasia, particularly in patients with longstanding symptoms. Future research should investigate whether mast cells play direct or indirect modulatory roles in the development and progression of human tendinosis.Repetitive overuse tendon injury (tendinopathy) is a major burden on the healthcare system and a challenge to orthopaedic and sports medicine practitioners.1 Clinical symptoms include pain, swelling, and impaired function. Despite the increased vascular flow and vascular hyperplasia that characterise tendinosis, an acute cellular inflammation (neutrophils, macrophages, lymphocytes) is rarely reported in the chronic stages. This lack of typical acute inflammatory cells has led to increasing adoption of the term ''tendinosis'' as opposed to ''tendonitis''. 4 Recently, Schubert et al 5 compared the numbers of CD68+ macrophages, CD3+ T lymphocytes, CD20+ B lymphocytes, and granulocytes in 10 patients with Achilles tendinosis and 10 patients with an acutely ruptured Achilles tendon. In this study, patients with tendinosis displayed increased numbers of macrophages and lymphocytes in association with hypervascular tissue, whereas patients with acutely ruptured tendon displayed greater numbers of granulocytes.5 Thus, inflammatory and reparative cell types may play a role in the pathogenesis of tendinosis and the development of vascular hyperplasia in chronic tendon lesions.Along with macrophages and lymphocytes, mast cell numbers are also known to be increased in a variety of chronic inflammatory or fibrotic disorders. In addition to their well known physiological role in triggering allergic reactions, mast cells release a variety of vasoactive, angiogenic and profibrotic substances that are either stored in granules or synthesised de novo in response to hypo...

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Section: Discussionmentioning

confidence: 88%

Increased mast cell numbers in human patellar tendinosis: correlation with symptom duration and vascular hyperplasia

et al. 2008

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“…34 These finding support the findings of early neovascularization and neuro sprouting in tendinosis lesions. 2,55 …”

Section: Introductionmentioning

confidence: 99%

Tendinosis

Kaeding¹,

Best

2009

Sports Health: A Multidisciplinary Approach

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Tendinosis is a troublesome clinical entity affecting many active people. Its treatment remains a challenge to sports medicine clinicians. The etiopathophysiology of tendinosis has not been well delineated. The known pathophysiology and the recent advances in the understanding of the etiologic process of tendinosis are discussed here, including new concepts in mechanotransduction and the biochemical alterations that occur during tendon overload. The optimal, nonoperative treatment of tendinosis is not clear. This article reviews recent evidence of the clinical efficacy of the following interventions: eccentric exercise, extracorporal shock wave treatment, corticosteroid and nonsteroidal anti-inflammatory medications, sclerosing injections, nitric oxide, platelet-rich plasma injections, and matrix metalloproteinase inhibitors. Eccentric exercise has strongest evidence of efficacy. Extracorporal shock wave treatment has mixed evidence and needs further study of energy and application protocols. Sclerosing agents show promising early results but require long-term studies. Corticosteroid and nonsteroidal anti-inflammatory medications have not been shown to be effective, and many basic science studies raise possible concerns with their use. Nitric oxide has been shown in several basic science studies to be promising, but clinical efficacy has not been well established. More clinical trials are needed to assess dosing, indications, and clinical efficacy of nitric oxide. Platelet-rich plasma injections have offered encouraging short-term results. Larger and longer-term clinical trials are needed to assess this promising modality. Matrix metalloproteinase inhibitors have had few clinical studies, and their role in the treatment of tendinosis is still in the early phase of investigation.

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“…NGF is produced by a number of cell types including mast cells [5,6,7], keratinocytes [8], and lymphocytes [9]. It induces mast cell degranulation [10, 11], growth and the differentiation of connective tissue-type mast cells from myeloid progenitors with IL-3 [12], enhances the survival and colony-forming ability of mast cells in a murine model [13, 14], upregulates FcεRI expression, intracellular tryptase activity and histamine content [15], and induces NFAT activation and chemokine production [16] in HMC-1 cells.…”

Section: Introductionmentioning

confidence: 99%

Granule Formation in NGF-Cultured Mast Cells Is Associated with Expressions of Pyruvate Kinase Type M2 and Annexin I Proteins

Kim

Ro³

2008

Int Arch Allergy Immunol

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Background: Nerve growth factor (NGF) is a potent mediator, which regulates characteristics of mast cells, but its biological function is not well characterized. This study aimed to screen proteins associated with the maturation of human mast cells-1 (HMC-1) or mouse bone marrow-derived mast cells (BMMCs) cultured with NGF, and to examine the functions of proteins involved. Methods: NGF (10 ng/ml) was added to cell culture medium every other day for 10 days for HMC-1 or twice a week for 5 weeks for BMMCs. Granule formation was determined by electron microscopy or May-Grünwald-Giemsa staining, TNF-α by ELISA, expressions of various proteins by two-dimensional gel electrophoresis (2-DE), siRNA transfection by Lipofectamine 2000, and the expressions of pyruvate kinase and annexin I by immunoblotting. Results: After NGF treatment, granule formation and total amounts of granular mediator, TNF-α increased in both mast cells. This TNF-α was released by calcium ionophore or by antigen/antibody reaction. Expressions of pyruvate kinase and annexin I obtained by 2-DE were confirmed by immunoblotting and siRNA-transfected HMC-1 cells. Expressions of proteins, granule formation and TNF-α content were blocked by both the TrkA inhibitor, K252a, and the ERK inhibitor, PD98059, but not by the PI3 kinase inhibitors, LY294002 and wortmannin. Conclusion: These data suggest that pyruvate kinase and annexin I expressed by NGF contribute to granule formation containing TNF-α as well as other mediators in mast cells, which play a major role in allergic diseases via a TrkA/ERK pathway.

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Nerve Growth Factor Immunoreactivity of Mast Cells in Acute Involuted Human Thymus

Cited by 7 publications

References 32 publications

Increased mast cell numbers in human patellar tendinosis: correlation with symptom duration and vascular hyperplasia

Increased mast cell numbers in human patellar tendinosis: correlation with symptom duration and vascular hyperplasia

Tendinosis

Granule Formation in NGF-Cultured Mast Cells Is Associated with Expressions of Pyruvate Kinase Type M2 and Annexin I Proteins

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