Increased Granzyme A Expression in Type II Pneumocytes of Patients with Severe Chronic Obstructive Pulmonary Disease

Vernooy, Juanita H. J.; Möller, Gertrude M.; Suylen, Robert Jan van; Spijk, Marlies P. van; Cloots, Roy H. E.; Hoet, Peter; Pennings, Herman Jan; Wouters, Emiel F.M.

doi:10.1164/rccm.200602-169oc

Cited by 69 publications

(56 citation statements)

References 32 publications

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“…In the past, gene expression studies using archival material have been limited to analysis of few targets (o4) in any given experiment. [10][11][12][13] Limited quantities available from archival material become a greater issue when microdissection is introduced. While it is possible to repeat the preparation and microdissection using serial sections, this is time consuming and labour intensive, and requires pooling of extracts to achieve uniformity in analysis.…”

Section: Preamplification and Endogenous Controlmentioning

confidence: 99%

A molecular expression signature distinguishing follicular lesions in thyroid carcinoma using preamplification RT-PCR in archival samples

et al. 2007

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Follicular variant of papillary thyroid carcinoma is a lesion that frequently causes difficulties from a diagnostic perspective in the laboratory. The purpose of this study was to interrogate a cohort of archival thyroid lesions using gene expression analysis of a panel of markers proposed to have utility as adjunctive markers in the diagnosis of thyroid neoplasia and follicular variant of papillary thyroid carcinoma in particular. Laser Capture Microdissection was used to procure pure cell populations for extraction. In addition a novel, multiplex preamplification technique was used to facilitate analysis of multiple targets. The panel comprised: HLA-DMA, HLA-DBQ1, CD74, CSNK1G2, IRF3, KRAS2, LYN, MT1K, MT1X, RAB23, TGFB1 and TOP2A, with CDKN1B as an endogenous control. Expression profiles for each target were generated using TaqMan s Real-Time PCR. HLA-DMA, HLA-DQB1, MT1X, CSNK1G2 and RAB23 were found to be differentially expressed (Po0.05) when comparing follicular adenoma and follicular variant of papillary thyroid carcinoma. Comparison of follicular adenoma and follicular thyroid carcinoma groups showed significant differential expression for MT1K, MT1X and RAB23 (Po0.05). Comparison of the papillary thyroid carcinoma group (classic and follicular variants) and the follicular adenoma group showed differential expression for CSNK1G2, HLA-DQB1, MT1X and RAB23 (Po0.05). Finally, KRAS2 was found to be differentially expressed (Po0.05) when comparing the papillary thyroid carcinoma and follicular thyroid carcinoma groups. This panel of molecular targets discriminates between follicular adenoma, papillary thyroid carcinoma, follicular variant of papillary thyroid carcinoma and follicular thyroid carcinoma by their expression repertoires. It may have utility for broader use in the setting of fine-needle aspiration cytology and could improve the definitive diagnosis of certain categories of thyroid malignancy.

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Section: Preamplification and Endogenous Controlmentioning

confidence: 99%

A molecular expression signature distinguishing follicular lesions in thyroid carcinoma using preamplification RT-PCR in archival samples

et al. 2007

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“…14 Immunohistological studies of COPD lung tissue localized GrB-positive CTL and GrA-positive NK cells in bronchial and alveolar walls. 15 Interestingly, GrA and GrB were also identified in alveolar macrophages and in type II pneumocytes of control and COPD patients (Table 1). However, no significant differences in GrA-and GrB-positive immune cells were found between COPD patients and the control group, whereas GrA staining in type II pneumocytes was significantly greater in COPD patients when quantified using immunolabeling but not by mRNA levels.…”

Section: Granzyme-induced Apoptosis In Diseasementioning

confidence: 96%

“…However, no significant differences in GrA-and GrB-positive immune cells were found between COPD patients and the control group, whereas GrA staining in type II pneumocytes was significantly greater in COPD patients when quantified using immunolabeling but not by mRNA levels. 15 The lack of a significant difference in granzyme expression was explained by the fact that the morphologically 'normal' tissues used as controls were obtained from lung cancer patients in which elevated GrA and GrB would be expected. 15 Unfortunately perforin expression was not assessed in this study so it is unclear as to whether type II pneumocytes that express granzymes are capable of inducing granzyme/perforin-induced cell death.…”

Section: Granzyme-induced Apoptosis In Diseasementioning

confidence: 99%

“…15 The lack of a significant difference in granzyme expression was explained by the fact that the morphologically 'normal' tissues used as controls were obtained from lung cancer patients in which elevated GrA and GrB would be expected. 15 Unfortunately perforin expression was not assessed in this study so it is unclear as to whether type II pneumocytes that express granzymes are capable of inducing granzyme/perforin-induced cell death.…”

Section: Granzyme-induced Apoptosis In Diseasementioning

confidence: 99%

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Granzymes in age-related cardiovascular and pulmonary diseases

et al. 2010

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Chronic inflammation is a hallmark of age-related cardiovascular and pulmonary diseases. Granzymes are a family of serine proteases that have been traditionally viewed as initiators of immune-mediated cell death. However, recent findings suggest that the pathophysiological role of granzymes is complex. Emerging functions for granzymes in extracellular matrix degradation, autoimmunity, and inflammation suggests a multifactorial mechanism by which these enzymes are capable of mediating tissue damage. Recent discoveries showing that granzymes can be produced and secreted by nonimmune cells during disease provide an additional layer of intricacy. This review examines the emerging biochemical and clinical evidence pertaining to intracellular and/or extracellular granzymes in the pathogenesis of aging and cardiopulmonary diseases.

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“…This protease is believed to function by entering virus-infected cells and growing tumors via pores formed by perforin, which is also expressed in cytotoxic cells, and participating in the apoptosis induction of abnormal cells (Chowdhury and Lieberman 2008;Kam et al 2000). It has been found that GrA is also found in body fluids such as blood (Spaeny-Dekking et al 1998;Tremblay et al 2000) and that in the lung, GrA mRNA is expressed not only in cytotoxic lymphocytes infiltrating this tissue but also in alveolar type II epithelial cells and alveolar macrophages (Vernooy et al 2007). Importantly, GrA was found to promote release of inflammatory mediators such as interleukin (IL)-6 and IL-8 from cultured cell lines (Sower et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Granzyme A and thrombin differentially promote the release of interleukin-8 from alveolar epithelial A549 cells

et al. 2010

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Some of extracellular serine proteases with trypsin-like specificity of cleavage have been known to increase the release of inflammatory mediators from various cell types. For instance, two well-known trypsin-like serine proteases circulating in blood, granzyme A (GrA) and thrombin, have been found to promote interleukin (IL)-8 release from an alveolar epithelial A549 cell line. However, the mechanisms by which the proteases promote IL-8 release from the cells are not fully understood. In the present study, using A549 cells we found that (1) thrombin promoted IL-8 release from the cells via a mechanism partially involving activation of protease-activated receptor-1, a G-protein coupled receptor, whereas a recombinant form of GrA (rGrA) did it via a mechanism that does not involve the receptor activation; that (2) unlike rGrA, thrombin did not cause detachment and microtubule disruption of the cells; and that (3) the release of IL-8 induced by rGrA was inhibited in the presence of taxol, a microtubulestabilizing reagent, whereas that induced by thrombin was not. These findings suggest that rGrA and thrombin promote the release of IL-8 from A549 cells through distinct mechanisms.

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Increased Granzyme A Expression in Type II Pneumocytes of Patients with Severe Chronic Obstructive Pulmonary Disease

Abstract: GrA and GrB mRNA and protein are detectable in human lung tissue. GrA expression is increased in type II pneumocytes of patients with very severe COPD. These results indicate that GrA may be important in the development of COPD.

Cited by 69 publications

References 32 publications

A molecular expression signature distinguishing follicular lesions in thyroid carcinoma using preamplification RT-PCR in archival samples

A molecular expression signature distinguishing follicular lesions in thyroid carcinoma using preamplification RT-PCR in archival samples

Granzymes in age-related cardiovascular and pulmonary diseases

Granzyme A and thrombin differentially promote the release of interleukin-8 from alveolar epithelial A549 cells

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