Search results for "Integrin alpha M"
showing 10 items of 45 documents
The molecular basis of filamin binding to integrins and competition with talin.
2006
The ability of adhesion receptors to transmit biochemical signals and mechanical force across cell membranes depends on interactions with the actin cytoskeleton. Filamins are large, actin-crosslinking proteins that connect multiple transmembrane and signaling proteins to the cytoskeleton. Here, we describe the high-resolution structure of an interface between filamin A and an integrin adhesion receptor. When bound, the integrin beta cytoplasmic tail forms an extended beta strand that interacts with beta strands C and D of the filamin immunoglobulin-like domain (IgFLN) 21. This interface is common to many integrins, and we suggest it is a prototype for other IgFLN domain interactions. Notabl…
Identification of pH-regulated antigen 1 released from Candida albicans as the major ligand for leukocyte integrin alphaMbeta2.
2007
Candida albicans is a common opportunistic fungal pathogen and is the leading cause of invasive fungal disease in immunocompromised individuals. The induction of cell-mediated immunity to C. albicans is of critical importance in host defense and the prime task of cells of the innate immune system. We previously demonstrated that the integrin alpha(M)beta(2) (CD11b/CD18) is the major leukocyte receptor involved in C. albicans recognition, mediating both adhesive and migratory responses to the fungus. In the present study, we demonstrate that various C. albicans strains release a protease-sensitive activity into their conditioned medium that supports alpha(M)beta(2)-mediated cell adhesion and…
Differential effects of leflunomide on leukocytes: Inhibition of ratin vivo adhesion and humanin vitro oxidative burst without affecting surface mark…
1994
Leflunomide has been shown to combat effectively autoimmune diseases in a number of animal models, as well as chronic polyarthritis of humans. Here we report on the effects of this novel drug on the adherence of leukocytes to endothelium, an essential event in establishment and maintenance of inflammation. The entry of cells into tissues is dependent on interactions of adhesion molecules. The process of diapedesis, which these molecules control, involves three phases: tethering, triggering of receptors on endothelial cells and firm attachment of leukocytes to these cells. The interaction of LECAM-1 (constitutively expressed on circulating leukocytes) and P- and E-selectins on the vessel wll…
Structural and functional analysis of integrin alpha2I domain interaction with echovirus 1.
2004
Integrins are cell surface receptors for several microbial pathogens including echovirus 1 (EV1), a picornavirus. Cryo-electron microscopy revealed that the functional domain (alpha(2)I) of human alpha(2)beta(1) integrin binds to a surface depression on the EV1 capsid. This three-dimensional structure of EV1 bound to alpha(2)I domain provides the first structural details of an integrin interacting with a picornavirus. The model indicates that alpha(2)beta(1) integrin cannot simultaneously bind both EV1 and the physiological ligand collagen. Compared with collagen binding to the alpha(2)I domain, the virus binds with a 10-fold higher affinity but in vitro uncoating of EV1 was not observed as…
Contribution of bronchial biopsies in the evaluation of pathogenesis and progression of COPD.
2016
This review summarizes and discusses the lung pathology of COPD patients emphasising on inflammatory cell phenotypes and mechanisms which prevail in different clinical conditions. In bronchial biopsies a series of events takes place during the progression of the disease from mild to severe. T-lymphocytes, particularly CD8+ cells and macrophages are the prevalent inflammatory cells in the lungs of healthy smokers and patients with mild/moderate COPD. This T-cell activation seems to be sustained by CD4+, CD8+ cells and macrophages expressing transcription factors and Tc1 cytokines such as NF-kB, STAT4 and IFNγ. In contrast, severe disease is characterized by lymphocytes producing greater amo…
A Raft-derived, Pak1-regulated Entry Participates in α2β1 Integrin-dependent Sorting to Caveosomes
2008
We have previously shown that a human picornavirus echovirus 1 (EV1) is transported to caveosomes during 2 h together with its receptor alpha2beta1 integrin. Here, we show that the majority of early uptake does not occur through caveolae. alpha2beta1 integrin, clustered by antibodies or by EV1 binding, is initially internalized from lipid rafts into tubulovesicular structures. These vesicles accumulate fluid-phase markers but do not initially colocalize with caveolin-1 or internalized simian virus 40 (SV40). Furthermore, the internalized endosomes do not contain glycosylphosphatidylinositol (GPI)-anchored proteins or flotillin 1, suggesting that clustered alpha2beta1 integrin does not enter…
Cross Talk between β1and αVIntegrins: β1Affects β3mRNA Stability
2001
There is increasing evidence that a fine-tuned integrin cross talk can generate a high degree of specificity in cell adhesion, suggesting that spatially and temporally coordinated expression and activation of integrins are more important for regulated cell adhesive functions than the intrinsic specificity of individual receptors. However, little is known concerning the molecular mechanisms of integrin cross talk. With the use of β1-null GD25 cells ectopically expressing the β1A integrin subunit, we provide evidence for the existence of a cross talk between β1and αVintegrins that affects the ratio of αVβ3and αVβ5integrin cell surface levels. In particular, we demonstrate that a down-regulati…
Rôle de l’inflammasome dans les pathologies cardiovasculaires
2011
NOD-like receptors (NLRs) constitute a recently identified family of intracellular pattern recognition receptors which contains more than 20 members in mammals. Some of the NLRs, the NALP subfamily, constituted from 14 members, many of them without actual identified role, form multiproteic complex known as inflammasome, that initiate inflammation by processing inactive pro-caspase-1 to its active form, allowing the cleavage and subsequent activation of pro-IL-1β and pro-IL-18. We review the identified roles of NLRs in pathologies and argue for the role of inflammasome in the development of cardiovascular diseases. The atherogenic cytokines IL-1β and IL-18 are matured in NLRPs inflammasomes.…
Integrin α2β1 Mediates Isoform-Specific Activation of p38 and Upregulation of Collagen Gene Transcription by a Mechanism Involving the α2 Cytoplasmic…
1999
Two collagen receptors, integrins alpha1beta1 and alpha2beta1, can regulate distinct functions in cells. Ligation of alpha1beta1, unlike alpha2beta1, has been shown to result in recruitment of Shc and activation of the Ras/ERK pathway. To identify the downstream signaling molecules activated by alpha2beta1 integrin, we have overexpressed wild-type alpha2, or chimeric alpha2 subunit with alpha1 integrin cytoplasmic domain in human osteosarcoma cells (Saos-2) lacking endogenous alpha2beta1. The chimeric alpha2/alpha1 chain formed a functional heterodimer with beta1. In contrast to alpha2/alpha1 chimera, forced expression of alpha2 integrin resulted in upregulation of alpha1 (I) collagen gene …
CD11b Regulates Fungal Outgrowth but Not Neutrophil Recruitment in a Mouse Model of Invasive Pulmonary Aspergillosis
2019
Abstract Background and Aims: In immunosuppressed individuals Aspergillus (A.) fumigatus is a frequent cause of invasive pulmonary aspergillosis (IPA) which is highly associated with relevant morbidity and mortality. Moreover, it often occurs in patients suffering from leukocyte-adhesion deficiency type 1 (LAD1) which is triggered by a functional loss of CD18 in ß2 integrin receptors as these receptors consist of an alpha subunit (CD11a-CD11d) and CD18 as the common beta subunit. ß2 integrin receptors are differentially expressed by leukocytes, and are required for cell-cell interaction, transendothelial migration, uptake of opsonized pathogens, and cell signaling processes. Here, we asked …