Neutrophil heterogeneity was described decades ago, but it could not be elucidated at the time whether existence of different neutrophil subsets had any biological relevance. It has been corroborated in recent years that subsets, defined by differential expression various markers, are indeed present human blood, calling for renewed attention to this question. The granule protein olfactomedin 4 (OLFM4) suggested define two such subsets. We confirm simultaneous presence one OLFM4-positive and...

Fusobacterium nucleatum is a gram-negative and anaerobic oral commensal that implicated in inflammatory conditions of the tooth-supporting structures, is, periodontal diseases. One main characteristics these an accumulation neutrophil granulocytes gingival pockets where bacteria reside. Neutrophils are recruited to tissue-residing microbes by gradients derived chemoattractants, cellular migration over pocket epithelium into likely governed chemoattractants released amino acid fermenting...

Alpha-1-antitrypsin (A1AT) is an important inhibitor of neutrophil proteases including elastase, cathepsin G, and proteinase 3. Transcription profiling data suggest that A1AT expressed by human granulocytes during all developmental stages. has hitherto only been found associated with azurophile granules in neutrophils indicative expression being restricted to the promyelocyte stage. We examined localization production healthy donor be a constituent granule subtypes released from following...

Most notable among the acute phase proteins is serum amyloid A (SAA), levels of which can increase 1000-fold during infections, aseptic inflammation, and/or trauma. Chronically elevated SAA are associated with a wide variety pathological conditions, including obesity and rheumatic diseases. Using recombinant hybrid two human isoforms (SAA1 2) that does not exist in vivo, numerous vitro studies have given rise to notion pro-inflammatory molecule cytokine-like properties. It however unclear...

Neutrophils have the ability to capture and kill microbes extracellularly through formation of neutrophil extracellular traps (NETs). These are DNA protein structures that neutrophils release believed function as a defense mechanism against microbes. The classic NET process, triggered by, e.g., bacteria, fungi, or by direct stimulation kinase C phorbol myristate acetate, is an active process takes several hours relies on production reactive oxygen species (ROS) further modified...

Chronic granulomatous disease (CGD) is caused by mutations in genes that encode the NADPH-oxidase and result a failure of phagocytic cells to produce reactive oxygen species (ROS) via this enzyme system. Patients with CGD are highly susceptible infections often suffer from inflammatory disorders; latter occurs absence infection correlates spontaneous production cytokines. This clinical feature suggests NADPH-oxidase-derived ROS not required for, or may even suppress, processes. Experimental...

Abstract Neutrophil apoptosis is important for the termination of inflammatory reactions, in that it ensures placid clearance these potently cytotoxic cells. Various proinflammatory cytokines delay neutrophil apoptosis, which may result accumulation cells, sometimes accompanied by tissue destruction, potentially leading to various disease states. Rheumatoid arthritis (RA) characterized frequently elevated levels acute-phase reactant serum amyloid A (SAA) circulation and tissues. SAA emerging...

ABSTRACT The virulence and pathogenesis mechanisms of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains depend on a newly described group phenol-soluble modulin (PSM) peptides (the PSMα peptides) with cytolytic activity. These toxins are α-helical formyl at the N terminus, they activate neutrophils through peptide receptor 2 (FPR2), function closely correlated to capacity staphylococcal species cause invasive infections. effects two synthetic were...

Neutrophils express different chemoattractant receptors of importance for guiding the cells from blood stream to sites inflammation. These communicate with one another, a cross talk manifested as hierarchical, heterologous receptor desensitization. We describe new mechanism, by which desensitized formyl peptide (FPRdes) can be reactivated. FPR desensitization is induced through binding specific agonists and reached after short period active signaling. The mechanism that transfers...

Recent technical advances in the extraction of dermal interstitial fluid (ISF) have stimulated interest using this rather unexploited biofluid as an alternative to blood for detection and prediction disease. However, knowledge about presence useful biomarkers health monitoring ISF is still limited. In study, we characterized lipidome human suction blister (SBF) a surrogate pure compared it that plasma.Plasma SBF samples were obtained from 18 healthy volunteers after overnight fast. Total...

ABSTRACT LL-37 is a cationic host defense peptide that highly expressed during acute inflammation and kills bacteria by poorly defined mechanisms, resulting in permeabilization of microbial membranes. High concentrations have also been reported to cytotoxic effects against eukaryotic cells, but the clearly capable differentiating between membranes with different compositions (eukaryotic versus bacterial membranes). Eukaryotic cells such as leukocytes change their membrane composition...

Objective Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory disease of unknown etiology that primarily affects preschool‐aged children. PFAPA characterized by recurrent attacks fever symptoms inflammation consistent with the acronym. Since diseases are, definition, mediated cells innate immune system, aim this study was to evaluate functional features neutrophils, most abundant cell in circulation, children syndrome. Methods Blood...

Upon infection with Mycobacterium tuberculosis, neutrophils are massively recruited to the lungs, but role of these cells in combating is poorly understood. Through a type VII secretion system, M. tuberculosis releases heterodimeric protein complex, containing 6-kDa early secreted antigenic target (ESAT-6) and 10-kDa culture filtrate (CFP-10), that essential for virulence. Whereas ESAT-6 component possesses multiple virulence-related activities, no direct biological activity CFP-10 has been...

Formyl peptide receptor 2 (FPR2) is a G protein-coupled pattern recognition sensing both mitochondrial- and bacterial-derived formylated peptides, including the PSMα toxins secreted by community-associated methicillin-resistant Staphylococcus aureus strains. Similar to many other FPR2 agonistic nanomolar concentrations of PSMα2 PSMα3 activate neutrophils increase cytosolic concentration Ca2+ release NADPH oxidase-derived reactive oxygen species. In addition, peptides induce homologous...

Background. Biomarker analysis allows for the detection and prediction of disease as well health monitoring. The use interstitial fluid (ISF) a matrix biomarkers has recently gained interest. This study aimed to compare levels inflammatory markers in ISF from suction blister (SBF) plasma. Methods. Plasma SBF were collected 18 healthy individuals. Samples analyzed 92 inflammation-related protein by Proximity Extension Assay (PEA). Protein profiles two matrices compared using traditional...

Abstract Neutrophils are capable of producing significant amounts reactive oxygen species (ROS) by the phagocyte NADPH oxidase, which consists membrane-bound and cytoplasmic subunits that assemble during activation. harbor two distinct pools membrane-localized oxidase components, one expressed in plasma membrane membranes intracellular granules. Assembly active at either type leads to release extracellular ROS or production inside compartments, respectively. The subunit p40phox seems...

In recent years, the concept of distinct subpopulations human neutrophils has attracted much attention. One bona fide subset marker, exclusively expressed by a proportion circulating in given individual, and therefore dividing two subpopulations, is glycoprotein CD177. CD177 on plasma granule membranes 0-100% depending donor. Several vitro studies have linked to neutrophil transmigration, yet very few looked at role for tissue recruitment vivo. We investigate whether CD177+ CD177- subsets...

There is incomplete mechanistic understanding of the mobilization neutrophils in systemic and local compartment smokers with chronic obstructive pulmonary disease (COPD). In this pilot study, we characterized how adhesion molecules CD11b CD62L, surface markers indicative priming, are altered as extravasate, whether density CD62L differs between long-term tobacco (LTS) without COPD compared healthy never-smokers (HNS). Unstimulated blood from LTS (<i>n</i> = 5) 9) displayed lower...

Short-lived neutrophils are major players in inflammation, arriving early to infected and/or injured tissues. After performed duty, programmed die by apoptosis and thereafter rapidly cleared other phagocytes. In vitro, modulation of the apoptotic process has been thoroughly investigated isolated from peripheral blood, but less is known about regulation this derived extravascular We recently demonstrated that having transmigrated vivo, obtained experimental skin chambers healthy human...

Neutrophil migration from blood to tissue-residing microbes is governed by a series of chemoattractant gradients both endogenous and microbial origin. Periodontal disease characterized neutrophil accumulation in the gingival pocket, recruited subgingival biofilm consisting mainly gram-negative, anaerobic proteolytic species such as Porphyromonas gingivalis. The fact that neutrophils are dominating cell type pocket suggests neutrophil-specific chemoattractants released bacteria, but...

Interleukin-1 beta (IL-1β), a pro-inflammatory cytokine, has been ascribed role in the expansion of myeloid progenitors acute leukemia (AML) and promoting cell-induced suppression lymphocyte-mediated immunity against malignant cells. This study aimed at defining potential impact IL-1β post-remission phase AML patients receiving immunotherapy for relapse prevention an international IV trial 84 (ClinicalTrials.gov; NCT01347996). Consecutive serum samples were collected from first complete...