Lfa-1

Understanding cellular decisions due to receptor-ligand interactions at cell-cell interfaces has been hampered by the difficulty of independently varying the surface density of multiple different ligands. Here, we express the synthetic binder protein SpyCatcher, designed to form spontaneous covalent bonds with interactors carrying a Spytag, on the cell surface. Using this, we show that addition of different concentrations and combinations of native Spytag-fused ligands allows for the combinatorial display of ligands on cells within minutes...

The chemokine Cxcl1 plays a crucial role in recruiting neutrophils in response to infection. The early events in chemokine-mediated neutrophil extravasation involve a sequence of highly orchestrated steps - rolling, adhesion, arrest, and diapedesis. Cxcl1 function is determined by its properties of reversible monomer-dimer equilibrium and binding to Cxcr2 and glycosaminoglycans. Here, we characterized how these properties orchestrate extravasation using intravital microscopy of the cremaster. Compared to WT Cxcl1, that exists as both a monomer and a dimer, the trapped dimer caused faster rolling, less adhesion, and less extravasation...

Anti-PD-1 antibody therapy has achieved success in tumor treatment; however, the duration of its clinical benefits are typically short. The functional state of intratumoral CD8+ T cells substantially affects the efficacy of anti-PD-1 antibody therapy. Understanding how intratumoral CD8+ T cells change will contribute to the improvement in anti-PD-1 antibody therapy. In this study, we found that tumor growth was not arrested after the late administration of anti-PD-1 antibody and that the antitumor function of CD8+ T cells decreased with tumor progression...

BACKGROUND: Extracellular vesicles (EVs) are natural nano-carriers that possess the required crucial features of an ideal biomolecular delivery system. However, using unmodified EVs may have some limitations such as low accumulation in target sites. Studies have established that engineering EVs against different cell surface markers can overcome most of these hurdles. METHODS: In this study, engineered EVs expressing ICAM-1/LAMP2b fusion protein on their surfaces were produced and isolated...

Lymphocyte function-associated antigene-1 (LFA-1) is a well-described integrin found on lymphocytes and other leukocytes, which is known to be overexpressed in leukemias and lymphomas. This receptor plays a significant role in immune responses such as T-cell activation, leukocyte cell-cell interactions, and trafficking of leukocyte populations. Subsequently, binders of LFA-1 emerge as potential candidates for cancer and autoimmune therapy. This study used the phage display technique to construct and characterize a high-affinity single-chain fragment variable (scFv) antibody against LFA-1...

B cell antigen receptor (BCR) signaling induces actin cytoskeleton remodeling by stimulating actin severing, actin polymerization, and the nucleation of branched actin networks via the Arp2/3 complex. This enables B cells to spread on antigen-bearing surfaces in order to increase antigen encounters and to form an immune synapse (IS) when interacting with antigen-presenting cells (APCs). Although the WASp, N-WASp, and WAVE nucleation-promoting factors activate the Arp2/3 complex, the role of WAVE2 in B cells has not been directly assessed...

Natural killer (NK) cells patrol tissue to mediate lysis of virally infected and tumorigenic cells. Human NK cells are typically identified by their expression of neural cell adhesion molecule (NCAM, CD56), yet, despite its ubiquitous expression on NK cells, CD56 remains a poorly understand protein on immune cells. CD56 has been previously demonstrated to play roles in NK cell cytotoxic function and cell migration. Specifically, CD56-deficient NK cells have impaired cell migration on stromal cells and CD56 is localized to the uropod of NK cells migrating on stroma...

Leukocytes possess the ability to migrate upstream-against the direction of flow-on surfaces of specific chemistry. Upstream migration was first characterized in vitro for T-cells on surfaces comprised of intracellular adhesion molecule-1 (ICAM-1). Upstream migration occurs when the integrin receptor αL β2 (also known as lymphocyte function-associated antigen-1, or LFA-1) binds to ICAM-1. LFA-1/ICAM-1 interactions are ubiquitous and are widely found in leukocyte trafficking. Upstream migration would be employed after cells come to arrest on the apical surface of the endothelium and might confer an advantage for both trans-endothelial migration and tissue surveillance...

BACKGROUND: Parkinson's disease (PD), which is associated to autoimmune disorders, is characterized by the pathological deposition of alpha-synuclein (α-Syn) and loss of dopaminergic (DA) neurons. Th17 cells are thought to be responsible for the direct loss of DA neurons. C-C chemokine ligand 5 (CCL5) specifically induces Th17 cell infiltration into the SN. However, the specific effect of CCL5 on Th17 cells in PD and the relationship between CCL5 and lymphocyte function-associated antigen-1 (LFA-1) expression in Th17 cells are unknown...

BACKGROUND: Radiotherapy (RT) has been shown to effectively induce the expression of intercellular adhesion molecule-1 (ICAM-1) which is recognized by lymphocyte function-associated antigen 1 (LFA-1) expressed on NK cells. However, the potential synergistic antitumor immune response of tumor irradiation and administered NK cells has not been explored in intractable human liver cancers. Furthermore, NK cell targeting against both parental and cancer stemness has never been investigated...

BACKGROUND & OBJECTIVES: To examine β-D-mannuronic acid (M2000) effects on L-selectin shedding and leucocyte function-associated antigen-1 (LFA-1) expression as mechanisms of action of this drug in patients with ankylosing spondylitis (AS). METHODS: To investigate the molecular consequences of β-D-mannuronic acid on L-selectin shedding, flow cytometry method was used. Furthermore, the effect of it on LFA-1 gene expression was analyzed by using quantitative real time (qRT)-PCR technique...

Immune surveillance and adaptive immune responses, involving continuously circulating and tissue-resident T-lymphocytes, provide host defense against infectious agents and possible malignant transformation while avoiding autoimmune tissue damage. Activation, migration, and deployment of T-cells to affected tissue sites are crucial for mounting an adaptive immune response. An effective adaptive immune defense depends on the ability of T-cells to dynamically reprogram their metabolic requirements in response to environmental cues...

The mammalian Sterile 20-like kinase 1/2 (MST1/2) belongs to the serine/threonine (GC) protein kinase superfamily. Collective studies confirm the vital role MST1/2 in inflammation and immunity. MST1/2 is closely related to the progress of inflammation. Generally, MST1/2 aggravates the inflammatory injury through MST1-JNK, MST1-mROS, MST1-Foxo3, and NF-κB pathways, as well as several regulatory factors such as tumor necrosis factor-α (TNF-α), mitochondrial extension factor 1 (MIEF1), and lipopolysaccharide (LPS)...

The relationship between polyamines and healthy longevity has received much attention in recent years. However, conducting research without understanding the properties of polyamines can lead to unexpected pitfalls. The most fundamental consideration in conducting polyamine studies is that bovine serum used for cell culture contains bovine serum amine oxidase. Bovine serum amine oxidase, which is not inactivated by heat treatment, breaks down spermine and spermidine to produce the highly toxic aldehyde acrolein, which causes cell damage and activates autophagy...

BACKGROUND: Currently, no specific treatment is available for acute onset pancreatitis (AP), and management relies on symptomatic and supportive standard of care (SOC). Fuzapladib is a novel leukocyte function-associated antigen type-1 (LFA-1) activation inhibitor, blocking activation and subsequent adhesion and migration of neutrophils, potentially decreasing the risk of pancreatitis progression and systemic inflammation. OBJECTIVE: Evaluate the safety and clinical response of dogs with AP after 3 days of administration of fuzapladib...

UNLABELLED: T cells are important for the control of acute myeloid leukemia (AML), a common and often deadly malignancy. We observed that some AML patient samples are resistant to killing by human engineered cytotoxic CD4 + T cells. Single-cell RNA-seq of primary AML samples and CD4 + T cells before and after their interaction uncovered transcriptional programs that correlate with AML sensitivity or resistance to CD4 + T cell killing. Resistance-associated AML programs were enriched in AML patients with poor survival, and killing-resistant AML cells did not engage T cells in vitro ...

INTRODUCTION: Atherosclerosis is prevalent globally, closely associated with dyslipidemia and other metabolic dysfunction. Early diagnosis of atherosclerosis is challenging due to limited diagnostic capabilities that need to be expanded with animal models with enhanced vascular biology like rats. Our previous research showed [111In] In-DANBIRT has potential as a diagnostic tool for detecting atherosclerosis in mice. The primary aim of the present study is to evaluate [111In] In-DANBIRT in a novel atherosclerotic rat with early- and late-stage atherosclerosis and metabolic disease...

Postoperative ileus (POI) is a surgical complication that induces emesis and anorexia. Fuzapladib (FUZ), an inhibitor of leukocyte-function-associated antigen type 1 (LFA-1) activation, a leukocyte adhesion molecule, exerts anti-inflammatory effects by inhibiting leukocyte migration into the inflammatory site. In this study, we examined the prophylactic impact of FUZ on POI in a mouse model. POI model mice were generated by intestinal manipulation, and the effect of FUZ on intestinal transit and the infiltration of inflammatory cells into the ileal muscularis externa was assessed...

Immune checkpoint blockade (ICB) has become the standard of care for several solid tumors. Multiple combinatorial approaches have been studied to improve therapeutic efficacy. The combination of anti-angiogenesis agents and ICB has demonstrated efficacy in several cancers. To improve the mechanistic understanding of synergies with these treatment modalities, we performed serologic screens of human protein array using sera from long-term responding patients treated with ipilimumab and bevacizumab. We discovered a high-titer antibody response against EDIL3 that correlated with favorable clinical outcomes...

Cancer immunotherapy has been proven to be clinically effective in multiple types of cancers. Lymphocyte function-associated antigen 1 (LFA-1), a member of the integrin family of adhesion molecules, is expressed mainly on αβ T cells. LFA-1 is associated with tumor immune responses, but its exact mechanism remains unknown. Here, two kinds of mice tumor model of LFA-1 knockout (LFA-1-/- ) mice bearing subcutaneous tumor and Apc Min/+ ;LFA-1-/- mice were used to confirm that LFA-1 knockout resulted in inhibition of tumor growth...