Differential integrin expression by T lymphocytes: Potential role in DMD muscle damage

Pinto‐Mariz, Fernanda; Carvalho, Lydston Rodrigues de; Mello, Wallace de; Araújo, Alexandra de Queiroz Campos; Ribeiro, Márcia Gonçalves; Cunha, Maria do Carmo Soares Alves; Voït, Thomas; Butler-Browne, Gillian; Silva-Barbosa, Suse Dayse; Savino, Wilson

doi:10.1016/j.jneuroim.2010.03.006

Cited by 13 publications

(16 citation statements)

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“…Basophil-enriched populations were also generated from total bone marrow cells cultured for 8 days with IL-3, as described before [8], [9]. Panel a depicts cytofluorometric profiles of constitutively expressed integrin-type ECM receptors for type-1 collagen, fibronectin and laminin, on basophils isolated ex vivo or from IL-3-driven cultures.…”

Section: Resultsmentioning

confidence: 99%

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Mouse Basophils Reside in Extracellular Matrix-Enriched Bone Marrow Niches Which Control Their Motility

et al. 2013

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Basophils co-express FcεRIα and CD49b, the α-2 chain of integrin-type receptor VLA-2 (α2β1), which recognizes type-1 collagen as a major natural ligand. The physiological relevance of this integrin for interactions with extracellular bone marrow matrix remains unknown. Herein, we examined the expression of several receptors of this family by bone marrow-derived basophils sorted either ex-vivo or after culture with IL-3. Having established that both populations display CD49d, CD49e and CD49f (α-4, α-5 and α-6 integrins subunits, respectively), we addressed receptor functions by measuring migration, adhesion, proliferation and survival after interacting with matched natural ligands. Type I collagen, laminin and fibronectin promoted basophil migration/adhesion, the former being the most effective. None of these ligands affected basophil viability and expansion. Interactions between basophils and extracellular matrix are likely to play a role in situ, as supported by confocal 3D cell imaging of femoral bone marrow sections, which revealed basophils exclusively in type-1 collagen-enriched niches that contained likewise laminin and fibronectin. This is the first evidence for a structure/function relationship between basophils and extracellular matrix proteins inside the mouse bone marrow.

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Section: Resultsmentioning

confidence: 99%

“…Six μm thick femoral cryostat sections were assessed for simultaneous expression of CD49b, FcεRIα and one given ECM protein, as reported before [9], [10]. After nuclear staining with DAPI, samples were analyzed under a confocal fluorescence microscope (TCS SP5, Leica, Germany).…”

Section: Methodsmentioning

confidence: 99%

Mouse Basophils Reside in Extracellular Matrix-Enriched Bone Marrow Niches Which Control Their Motility

et al. 2013

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“…Varios estudos tem demonstrado que macrófagos e linfócitos T CD4 + são as principais células do sistema imune que se infiltram no músculo ditrófico (ARAHATA; ENGEL, 1988a,b;McDOUALL;DUNN;DUBOWITZ, 1990;GOROSPE et al, 1994;CONFALONIERI et al, 2003;PINTO-MARIZ et al, 2010).…”

Section: Discussaounclassified

“…PORTER et al, 2001PORTER et al, , 2003CONFALONIERI et al, 2003;BORIEK, 2003;LEE;TIDBALL, 2004;CHEN et al, 2005;TIDBALL, 2005;ACHARYYA et al, 2007;VIDAL et al, 2008;EVANS et al, 2009b;PINTO-MARIZ et al, 2010).…”

Section: Discussaomentioning

confidence: 99%

“…Além disso, também relataram síndrome de má absorção e processos diarréicos atribuídos à disfunção pancreática em humanos e alterações estruturais e/ou funcionais em outros órgãos nos demais modelos de estudo (NOWAK; IONASESCU; ANURAS, 1982;BAROHN et al, 1988;MIYATAKE et al, 1989;GRANDO et al, 2009;ABREU et al, 2012 WEHLING et al, 2001;EVANS et al, 2009b DUBOWITZ, 1990;GOROSPE et al, 1994;. CONFALONIERI et al, 2003;PINTO-MARIZ et al, 2010).…”

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Imunomodulação in vitro das células tronco mesenquimais em cães da raça golden retriever sadios e afetados pela distrofia muscular

Abreu¹

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Flow Cytometry-Defined CD49d Expression in Circulating T-Lymphocytes Is a Biomarker for Disease Progression in Duchenne Muscular Dystrophy

Savino¹,

Pinto‐Mariz²,

Mouly³

2017

Methods in Molecular Biology

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Duchenne muscular dystrophy (DMD) affects 1:3500-1:5000 male births, and is caused by X-linked mutations in the dystrophin gene, manifested by progressive muscle weakness and wasting due to the absence of dystrophin protein, leading to degeneration of skeletal muscle. DMD patients are clinically heterogeneous and the functional phenotype often cannot be correlated with the genotype. Therefore, defined reliable noninvasive biomarkers aiming at predicting if a given DMD child will progress more or less rapidly will be instrumental to better design inclusion of defined patients for future therapeutic assays. We recently showed that CD49d expression levels in blood-derived T-cell subsets can predict disease progression in DMD patients. Herein we describe in detail the methodology to be applied for defining, through four-color flow cytometry, the membrane expression levels of the CD49d (the α4 chain of the integrins α4β1 and α4β7) in circulating CD4 and CD8 T cell subsets. Since we have also shown that this molecule can also be placed as a potential target for therapeutics in DMD, we also describe the cell migration functional assay that can be applied to test potential CD49d inhibitors that can modulate their ability to cross endothelial or extracellular matrix (ECM) barriers.

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Differential integrin expression by T lymphocytes: Potential role in DMD muscle damage

Cited by 13 publications

References 15 publications

Mouse Basophils Reside in Extracellular Matrix-Enriched Bone Marrow Niches Which Control Their Motility

Mouse Basophils Reside in Extracellular Matrix-Enriched Bone Marrow Niches Which Control Their Motility

Imunomodulação in vitro das células tronco mesenquimais em cães da raça golden retriever sadios e afetados pela distrofia muscular

Flow Cytometry-Defined CD49d Expression in Circulating T-Lymphocytes Is a Biomarker for Disease Progression in Duchenne Muscular Dystrophy

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