Cd11b

Blood ; 18 : — A consistently increased mRNA expression of the adhesion receptor CD11b is a hallmark of cd11b reported genomewide gene expression changes in precursor B-cell acute lymphoblastic leukemia PBC-ALL after 1 week of induction therapy. To investigate its clinical relevance, cd11b, CD11b protein expression in leukemic blasts has been cd11b measured at diagnosis patients and during therapy 53 patients, cd11b.

Federal government websites often end in. The site is secure. Macrophages are important for the first line of defense against microbial pathogens. Integrin CD11b, which is encoded by Itgam , is expressed on the surface of macrophages and has been implicated in adhesion, migration, and cell-mediated cytotoxicity. However, the functional impact of CD11b on the inflammatory responses of macrophages upon microbial infection remains unclear. Here, we show that CD11b deficiency resulted in increased susceptibility to sepsis induced by methicillin-resistant Staphylococcus aureus MRSA infection by enhancing the pro-inflammatory activities of macrophages.

Cd11b

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Myeloid cells are recruited to damaged tissues where they can resolve infections and tumor growth or stimulate wound healing and tumor progression. Recruitment of these cells is regulated by integrins, a family of adhesion receptors that includes integrin CD11b. Here we report that, unexpectedly, integrin CD11b does not regulate myeloid cell recruitment to tumors but instead controls myeloid cell polarization and tumor growth. CD11b activation promotes pro-inflammatory macrophage polarization by stimulating expression of microRNA Let7a. In contrast, inhibition of CD11b prevents Let7a expression and induces cMyc expression, leading to immune suppressive macrophage polarization, vascular maturation, and accelerated tumor growth. Pharmacological activation of CD11b with a small molecule agonist, Leukadherin 1 LA1 , promotes pro-inflammatory macrophage polarization and suppresses tumor growth in animal models of murine and human cancer.

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Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. The development of easily accessible tools for human immunophenotyping to classify patients into discrete disease endotypes is advancing personalized therapy.

Lupus nephritis LN is a common complication of systemic lupus erythematosus SLE with unclear etiology and limited treatment options. Immune cell infiltration into the kidneys, a hallmark of LN, triggers tissue damage and proteinuria. CD11b modulates several key biological functions in innate immune cells, including cell adhesion, migration, and phagocytosis. CD11b also modulates other signaling pathways in these cells, such as the Toll-like receptor signaling pathways, that mediate generation of type I interferons, a key proinflammatory cytokine and circulating biomarker in SLE and LN patients. However, how variants in ITGAM gene contribute to disease pathogenesis has not been completely established. Here, we provide an overview of CD11b modulated mechanisms and the functional consequences of the genetic variants that can drive disease pathogenesis. We also present recent insights from studies after pharmacological activation of CD11b.

Cd11b

Federal government websites often end in. The site is secure. Therefore, targeting MDSC recruitment or function is of significant interest as a strategy to treat patients with ICI-resistant cancer. Interestingly, activation of CD11b with leukadherin-1 was found to reduce macrophage and neutrophil migration in animal models of inflammatory conditions. Preclinical studies with GB, a salt form of leukadherin-1, demonstrated that activation of CD11b improves the antitumor immune response and enhances the response to immunotherapy in mouse models of pancreatic adenocarcinoma, breast cancer and lung cancer. Immune checkpoint inhibitors ICIs such as programmed cell death-1 PD-1 -blocking antibodies have revolutionized cancer therapy; however, not all tumors are sensitive to such treatments, with many patients refractory or developing resistance during treatment. MDSCs accumulate in tumor and lymphoid tissues of patients with cancer, and can differentiate into tumor-associated macrophages TAMs , which exhibit a wide spectrum of both tumor-inhibiting and tumor-promoting activities depending on the stimuli present.

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S2CID These differences may arise from the unique microenvironment cues and alterations in blood vessel biology observed in tumors versus inflamed tissue. Current Opinion in Cell Biology. Blood 18 : — Cd11b regulates fungal outgrowth but not neutrophil recruitment in a mouse model of invasive pulmonary aspergillosis. Rosetti, F. This suggests that CD11b negatively regulates innate immune cell activation downstream of TLR pathways, and misregulation of this key regulatory mechanism might underlie LN and SLE pathogenesis. Drug Discov. Show results from All journals This journal. Isolation of single cells from murine tumors Tumors were isolated, minced in a petri dish on ice and then enzymatically dissociated in Hanks Balanced Salt Solution containing 0. Translational Research. The predictive contribution of CD11b in the multiparametric setting was investigated with the binary logistic regression model.

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Furthermore, we observed increased transcriptional induction of IRF4, which depends on the regulation of PI3K-Akt signaling and facilitates metabolic reprogramming to support functional polarization of the regulatory macrophages Co-stimulatory pathways in lymphocyte regulation: the immunoglobulin superfamily. We further evaluated the effect of the CD11b cutoff values in context of other clinically relevant parameters available at diagnosis. Vedder, N. One hundred microliters of the culture medium were incubated with equal amount of Griess reagent Promega, Madison, WI, USA at room temperature for 10 min, and the absorbance was measured at nm using a microplate reader. These data imply that the increased sensitivity to sepsis upon MRSA infection might be largely due to the negative regulatory role of CD11b in pro-inflammatory macrophages. PI3-kinase gamma promotes Rap1a-mediated activation of myeloid cell integrin alpha4beta1, leading to tumor inflammation and growth. Anyone you share the following link with will be able to read this content:. However, patients categorized into the subgroups A and C were clearly distinguished by all calculation parameters see Supplementary Table S2 online. The sepsis seesaw: tilting toward immunosuppression. Written informed consent was obtained from all subjects prior to inclusion.