In Vivo Roles of Integrins During Leukocyte Development and Traffic: Insights from the Analysis of Mice Chimeric for α5, αv, and α4 Integrins

Arroyo, Alicia G.; Taverna, Daniela; Whittaker, Charles A.; Strauch, Ulrike; Bader, B.; Rayburn, Helen; Crowley, Denise; Parker, Christina M.; Hynes, Richard O.

doi:10.4049/jimmunol.165.8.4667

Cited by 71 publications

(66 citation statements)

References 34 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings are quite remarkable given the relatively minor reduction in IEL number observed in a E -deficient mice [6] and illuminate a hitherto under-appreciated redundancy in the integrin system for maintaining lymphocytes within the intestinal mucosa. Studies of chimeric a 5 -, a V -, or a 4 -null/recombinaseactivating gene (RAG)-2-deficient mice have demonstrated that these a subunits are not essential for maintaining normal IEL numbers in the small intestine [21]. However, a 1 -deficient mice are reported to have a 50% reduction in IEL number [13].…”

Section: Discussionmentioning

confidence: 99%

β1 integrins are not required for the maintenance of lymphocytes within intestinal epithelia

et al. 2005

View full text Add to dashboard Cite

b 1 integrins are thought to play a central role in maintaining lymphocytes within mucosal epithelia via their interactions with extracellular matrix proteins and subepithelial cellular components within and underlying the basement membrane. In the current study type a (CD8abTCRab) and type b (CD8aaTCRcd and CD8aaTCRab) intraepithelial lymphocyte (IEL) subsets within the mouse small intestine were found to express functional b 1 integrin and the b 1 integrin a chain partners a 1 , a 2 , and a 4 . Using inducible b 1 integrin-knockout bone marrow-chimeric mice we demonstrate that IEL expression of a 1 and a 2 but not a 4 is dependent on expression of the b 1 chain. Importantly, deletion of the b 1 chain in IEL did not alter the number or composition of lymphocytes within the intestinal epithelium. Thus, while IEL express functional b 1 integrins, these are not required to maintain lymphocytes within intestinal epithelia. This result is discussed in the light of conventional views of intestinal lymphocyte homing and localization.

show abstract

Section: Discussionmentioning

confidence: 99%

β1 integrins are not required for the maintenance of lymphocytes within intestinal epithelia

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Studies using mice chimeric for either the α4, α5, or αv subunit, which are the β1-associated α subunits on leucocyte progenitors, indicate that none of these integrins is required for colonization of the fetal haematopoietic organs but they do implicate α4 in the multilineage development of haematopoietic cells and in lymphocyte homing to lymph nodes and Peyer's patches [106,107]. Defective homing to Peyer's patches is also observed in mice deficient in β7, another β subunit with which α4 can combine to form the α4β7 integrin that recognizes MadCAM, an endothelial receptor expressed in the gut [108].…”

Section: Haematopoietic Cellsmentioning

confidence: 99%

Integrins in regulation of tissue development and function

Danen¹,

Sonnenberg²

2003

The Journal of Pathology

231

173

View full text Add to dashboard Cite

Cell adhesion is indispensable for embryonic development and for proper tissue function. In metazoans, integrins are the major adhesion receptors that connect cells to components of the extracellular matrix. Integrins are implicated in assembly of extracellular matrices, cell adhesion and migration on extracellular matrices, and in vertebrates (in which the integrin family has expanded) they can also mediate cell-cell adhesion. Furthermore, integrinmediated adhesion can modulate many different signal transduction cascades and support cell survival, proliferation, and influence the expression of differentiation-related genes. In this review we briefly explain how integrins can affect so many different aspects of cell behavior and discuss evidence for roles of integrins in tissue development, function, and disease.

show abstract

“…[73][74][75][76] However, studies with chimeric mice with homozygous deletions of integrin ␣ chains have not settled the role of individual integrin ␣ chains in stem cell homing, and it is possible that multiple receptors are involved. 14,[77][78] In vitro studies have shown a migration promoting activity for both laminin-10/11 and laminin-8 in tumor cell lines 22,79 and mouse integrin ␤2-deficient granulocytes. 55 We therefore here analyzed the effect of laminin-8 and laminin-10/11 on transmigration of CD34 ϩ cells stimulated with the chemokine SDF-1␣.…”

Section: Discussionmentioning

confidence: 99%

Laminin isoform–specific promotion of adhesion and migration of human bone marrow progenitor cells

Kortesmaa

Tryggvason

et al. 2003

Blood

110

View full text Add to dashboard Cite

Laminins are ␣␤␥ heterotrimeric extracellular proteins that regulate cellular functions by adhesion to integrin and nonintegrin receptors. Laminins containing ␣4 and ␣5 chains are expressed in bone marrow, but their interactions with hematopoietic progenitors are unknown. We studied human bone marrow cell adhesion to laminin-10/11 (␣5␤1␥1/␣5␤2␥1), laminin-8 (␣4␤1␥1), laminin-1 (␣1␤1␥1), and fibronectin. About 35% to 40% of CD34 ؉ and CD34 ؉ CD38 ؊ stem and progenitor cells adhered to laminin-10/11, and 45% to 50% adhered to fibronectin, whereas they adhered less to laminin-8 and laminin-1. Adhesion of CD34 ؉ CD38 ؊ cells to laminin-10/11 was maximal without integrin activation, whereas adhesion to other proteins was dependent on protein kinase C activation by 12-tetradecanoyl phorbol-13-acetate (TPA). Fluorescence-activated cell-sorting (FACS) analysis showed expression of integrin ␣6 chain on most CD34 ؉ and CD34 ؉ CD38 ؊ cells. Integrin ␣6 and ␤1 chains were involved in binding of both cell fractions to laminin-10/11 and laminin-8. Laminin-10/11 was highly adhesive to lineagecommitted myelomonocytic and erythroid progenitor cells and most lymphoid and myeloid cell lines studied, whereas laminin-8 was less adhesive. In functional assays, both laminin-8 and laminin-10/11 facilitated stromal-derived factor-1␣ (SDF-1␣)-stimulated transmigration of CD34 ؉ cells, by an integrin ␣6 receptor-mediated mechanism. In conclusion, we demonstrate laminin isoform-specific adhesive interactions with human bone marrow stem, progenitor, and more differentiated cells

show abstract

In Vivo Roles of Integrins During Leukocyte Development and Traffic: Insights from the Analysis of Mice Chimeric for α5, αv, and α4 Integrins

Abstract: Integrins 4 α , and v α , 5 α

Cited by 71 publications

References 34 publications

β1 integrins are not required for the maintenance of lymphocytes within intestinal epithelia

β1 integrins are not required for the maintenance of lymphocytes within intestinal epithelia

Integrins in regulation of tissue development and function

Laminin isoform–specific promotion of adhesion and migration of human bone marrow progenitor cells

Contact Info

Product

Resources

About