Abstract The chemokine CXCL1/MGSA plays a pivotal role in the host immune response by recruiting and activating neutrophils for microbial killing at tissue site. CXCL1 exists reversibly as monomers dimers, mediates its function binding glycosaminoglycans (GAG) CXCR2 receptor. We recently showed that both dimers are potent agonists, dimer is high-affinity GAG ligand, lysine arginine residues located two non-overlapping domains mediate interactions, there extensive overlap between...

The chemokine CXCL1 and its receptor CXCR2 play a crucial role in host immune response by recruiting activating neutrophils for microbial killing at the tissue site. Dysregulation this process has been implicated collateral damage causing disease. reversibly exists as monomers dimers, it proposed that distinct monomer dimer activities monomer-dimer equilibrium regulate neutrophil function. However, molecular mechanisms linking CXCL1/CXCR2 axis ‘beneficial' ‘destructive' phenotypes are not...

Abstract Chemokines play a crucial role in combating microbial infection by recruiting blood neutrophils to infected tissue. In mice, the chemokines Cxcl1/KC and Cxcl2/MIP2 fulfill this role. Cxcl1 Cxcl2 exist as monomers dimers, exert their function activating Cxcr2 receptor binding glycosaminoglycans (GAGs). Here, we characterized G protein β-arrestin activities, GAG heparan sulfate (HS) interactions of trapped dimeric variants. To understand how impact vivo function, neutrophil...

Platelet-derived chemokine CXCL7 (also known as NAP-2) plays a crucial role in orchestrating neutrophil recruitment response to vascular injury. exerts its function by activating the CXCR2 receptor and binding sulfated glycosaminoglycans (GAG) that regulate activity. exists monomers, dimers, tetramers, previous studies have shown monomer dominates at lower tetramer higher concentrations. These observations then raise question: what, if any, is of dimer? In this study, we make compelling...

Chemokine CXCL8 plays a pivotal role in host immune response by recruiting neutrophils to the infection site. exists as monomers and dimers, mediates recruitment interacting with glycosaminoglycans (GAGs) activating CXCR1 CXCR2 receptors. How monomer dimer interactions both receptors GAGs mediate trafficking is poorly understood. In particular, haptotactic (mediated GAG-bound chemokine) chemotactic soluble gradients have been implicated, whether it free or and/or that activates receptor...

Chemokines mediate diverse fundamental biological processes, including combating infection. Multiple chemokines are expressed at the site of infection; thus chemokine synergy by heterodimer formation may play a role in determining function. Chemokine function involves interactions with G-protein-coupled receptors and sulfated glycosaminoglycans (GAG). However, very little is known regarding structural features receptor GAG interactions. Solution nuclear magnetic resonance (NMR) molecular...

Abstract Microbial infection is characterized by release of multiple proinflammatory chemokines that direct neutrophils to the insult site. How collective function these orchestrates neutrophil recruitment not known. Here, we role for heterodimer and show Cxcl1–Cxcl2 a potent chemoattractant in mice can recruit more than individual chemokines. Chemokine-mediated determined Cxcr2 receptor signaling, endocytosis, binding glycosaminoglycans. We have now heterodimer's activity using cellular...

The early influx of neutrophils to the site infection may be an important step in host resistance against Mycobacterium tuberculosis. In this study, we investigated effect M. tuberculosis on ability guinea pig produce interleukin-8 (IL-8; CXCL8) and tumor necrosis factor alpha (TNF-alpha) activate alveolar macrophages. Neutrophils macrophages were isolated from naïve pigs, cultured together or alone, infected with virulent for 3, 12, 24 h. IL-8 protein production cocultures, as measured by...

Glycosaminoglycans (GAGs) bind a large array of proteins and mediate fundamental diverse roles in human physiology. Ion pair interactions between protein lysines/arginines GAG sulfates/carboxylates binding. Neutrophil-activating chemokines (NAC) are GAG-binding proteins, their sequences reveal high selectivity for lysines over arginines indicating they functionally not equivalent. NAC binding to GAGs impacts gradient formation, receptor functions, endothelial activation, which together...

The innate immune receptor Toll-like 3 (TLR3) can be present on the surface of plasma membranes cells and in endolysosomes. Unc93b1 protein has been reported to facilitate localization TLR7 9 is required for TLR3, -7, -9 signaling. We demonstrate that siRNA knockdown reduced abundance TLR3 cell without altering total accumulation. In addition, secretion ectodomain (T3ECD) into medium. Furthermore, two human single nucleotide polymorphisms affected herpesvirus influenza virus encephalopathy...

Chemokines mediate diverse functions from organogenesis to mobilizing leucocytes, and are unusual agonists for class-A GPCRs (G-protein-coupled receptors) because of their large size multi-domain structure. The current model receptor activation, which involves interactions between chemokine N-loop N-terminal residues (Site-I) extracellular loop/transmembrane (Site-II), fails describe differences in ligand/receptor selectivity the activation multiple signalling pathways. In present study, we...

CXCL17, a novel member of the CXC chemokine class, has been implicated in several human pathologies, but its role mediating immune response is not well understood. Characteristic features include resident macrophages orchestrating successive and structured recruitment neutrophils monocytes to insult site. Here, we show that Cxcl17 knockout (KO) mice, compared with littermate wild-type control were significantly impaired peritoneal neutrophil post-lipopolysaccharide (LPS) challenge. Further,...

Summary The guinea pig model of low-dose pulmonary tuberculosis has been used to study the pathogenesis infection as well mechanisms bacille Calmette–Guérin (BCG) vaccine-induced resistance. We investigated function lung cells from naive and BCG-vaccinated pigs after enzymatic digestion tissue with collagenase DNase I. total digest proliferated poorly purified protein derivative (PPD) but comparatively better ConA assessed by [3H]-thymidine uptake. However, non-adherent population obtained...

Arthritis is a musculoskeletal system disorder which involves destabilization of normal mechanisms. Due to changing habits living life, the number arthritic people will increase rapidly. Currently, existing anti-rheumatic drugs mostly show side effects like acne, blurred vision, high blood pressure and more effective reduce pain improve disease conditions but still, they do not treat completely. Literature available indicates that most seek complementary alternative treatments (CAM). Ginger...