Cytoplasmic Granules: Condensed areas of cellular material that may be bounded by a membrane.Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Granzymes: A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.Histocytochemistry: Study of intracellular distribution of chemicals, reaction sites, enzymes, etc., by means of staining reactions, radioactive isotope uptake, selective metal distribution in electron microscopy, or other methods.Neutrophil Infiltration: The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions.Annexin A3: A protein of the annexin family that catalyzes the conversion of 1-D-inositol 1,2-cyclic phosphate and water to 1-D-myo-inositol 1-phosphate.Mast Cells: Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the BASOPHILS, mast cells contain large amounts of HISTAMINE and HEPARIN. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the STEM CELL FACTOR.Staining and Labeling: The marking of biological material with a dye or other reagent for the purpose of identifying and quantitating components of tissues, cells or their extracts.Phagocytosis: The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Blood Proteins: Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes.Pore Forming Cytotoxic Proteins: Proteins secreted from an organism which form membrane-spanning pores in target cells to destroy them. This is in contrast to PORINS and MEMBRANE TRANSPORT PROTEINS that function within the synthesizing organism and COMPLEMENT immune proteins. These pore forming cytotoxic proteins are a form of primitive cellular defense which are also found in human LYMPHOCYTES.Perforin: A calcium-dependent pore-forming protein synthesized in cytolytic LYMPHOCYTES and sequestered in secretory granules. Upon immunological reaction between a cytolytic lymphocyte and a target cell, perforin is released at the plasma membrane and polymerizes into transmembrane tubules (forming pores) which lead to death of a target cell.Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin.Microscopy, Immunoelectron: Microscopy in which the samples are first stained immunocytochemically and then examined using an electron microscope. Immunoelectron microscopy is used extensively in diagnostic virology as part of very sensitive immunoassays.N-Formylmethionine Leucyl-Phenylalanine: A formylated tripeptide originally isolated from bacterial filtrates that is positively chemotactic to polymorphonuclear leucocytes, and causes them to release lysosomal enzymes and become metabolically activated.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Leukocytes: White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Killer Cells, Natural: Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.Cytotoxicity, Immunologic: The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.Chromaffin Granules: Organelles in CHROMAFFIN CELLS located in the adrenal glands and various other organs. These granules are the site of the synthesis, storage, metabolism, and secretion of EPINEPHRINE and NOREPINEPHRINE.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.RNA-Binding Proteins: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.Chemotaxis, Leukocyte: The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Secretory Vesicles: Vesicles derived from the GOLGI APPARATUS containing material to be released at the cell surface.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC Line: Established cell cultures that have the potential to propagate indefinitely.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Immunoenzyme Techniques: Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.T-Lymphocytes, Cytotoxic: Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Antigens, CD18: Cell-surface glycoprotein beta-chains that are non-covalently linked to specific alpha-chains of the CD11 family of leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE-ADHESION). A defect in the gene encoding CD18 causes LEUKOCYTE-ADHESION DEFICIENCY SYNDROME.Superoxides: Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.Chemotactic Factors: Chemical substances that attract or repel cells. The concept denotes especially those factors released as a result of tissue injury, microbial invasion, or immunologic activity, that attract LEUKOCYTES; MACROPHAGES; or other cells to the site of infection or insult.Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.Macrophage-1 Antigen: An adhesion-promoting leukocyte surface membrane heterodimer. The alpha subunit consists of the CD11b ANTIGEN and the beta subunit the CD18 ANTIGEN. The antigen, which is an integrin, functions both as a receptor for complement 3 and in cell-cell and cell-substrate adhesive interactions.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Interleukin-8: A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells.Cerebellum: The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.Pancreatic Elastase: A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25,000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. EC Adhesion: Adherence of cells to surfaces or to other cells.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Cell Degranulation: The process of losing secretory granules (SECRETORY VESICLES). This occurs, for example, in mast cells, basophils, neutrophils, eosinophils, and platelets when secretory products are released from the granules by EXOCYTOSIS.Leukotriene B4: The major metabolite in neutrophil polymorphonuclear leukocytes. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). (From Dictionary of Prostaglandins and Related Compounds, 1990)Leukocyte Count: The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells.Cathepsin G: A serine protease found in the azurophil granules of NEUTROPHILS. It has an enzyme specificity similar to that of chymotrypsin C.ZymosanComplement C5a: The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.Chemokine CXCL1: A CXC chemokine with specificity for CXCR2 RECEPTORS. It has growth factor activities and is implicated as a oncogenic factor in several tumor types.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.NADPH Oxidase: A flavoprotein enzyme that catalyzes the univalent reduction of OXYGEN using NADPH as an electron donor to create SUPEROXIDE ANION. The enzyme is dependent on a variety of CYTOCHROMES. Defects in the production of superoxide ions by enzymes such as NADPH oxidase result in GRANULOMATOUS DISEASE, CHRONIC.Receptors, Interleukin-8B: High-affinity G-protein-coupled receptors for INTERLEUKIN-8 present on NEUTROPHILS; MONOCYTES; and T-LYMPHOCYTES. These receptors also bind several other CXC CHEMOKINES.Lactoferrin: An iron-binding protein that was originally characterized as a milk protein. It is widely distributed in secretory fluids and is found in the neutrophilic granules of LEUKOCYTES. The N-terminal part of lactoferrin possesses a serine protease which functions to inactivate the TYPE III SECRETION SYSTEM used by bacteria to export virulence proteins for host cell invasion.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Dentate Gyrus: GRAY MATTER situated above the GYRUS HIPPOCAMPI. It is composed of three layers. The molecular layer is continuous with the HIPPOCAMPUS in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called GRANULE CELLS, whose AXONS pass through the polymorphic layer ending on the DENDRITES of PYRAMIDAL CELLS in the hippocampus.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Granulomatous Disease, Chronic: A defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. When chronic granulomatous disease is caused by mutations in the CYBB gene, the condition is inherited in an X-linked recessive pattern. When chronic granulomatous disease is caused by CYBA, NCF1, NCF2, or NCF4 gene mutations, the condition is inherited in an autosomal recessive pattern.Receptors, Formyl Peptide: A family of G-protein-coupled receptors that was originally identified by its ability to bind N-formyl peptides such as N-FORMYLMETHIONINE LEUCYL-PHENYLALANINE. Since N-formyl peptides are found in MITOCHONDRIA and BACTERIA, this class of receptors is believed to play a role in mediating cellular responses to cellular damage and bacterial invasion. However, non-formylated peptide ligands have also been found for this receptor class.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Myeloblastin: A polymorphonuclear leukocyte-derived serine protease that degrades proteins such as ELASTIN; FIBRONECTIN; LAMININ; VITRONECTIN; and COLLAGEN. It is named for its ability to control myeloid cell growth and differentiation.Chemokine CXCL2: A CXC chemokine that is synthesized by activated MONOCYTES and NEUTROPHILS. It has specificity for CXCR2 RECEPTORS.alpha-Defensins: DEFENSINS found in azurophilic granules of neutrophils and in the secretory granules of intestinal PANETH CELLS.
  • Moreover, a pool of Munc13-4 associated with mobilizable secondary and tertiary granules is relocalized to the plasma membrane after stimulation with fMLF. (
  • This adhesion defect resulted in a reduced adhesion-dependent activation of the respiratory burst and an increased chemotactic response of SIRPα-mutant neutrophils in vitro. (
  • In vitro activation of whole blood with fMLP caused similar changes in neutrophil light scatter, suggesting that neutrophil activation is present in peripheral blood of symptomatic asthmatic patients. (
  • These interactions promote MPO clearance, a reduction of nitric oxide and bradykinin levels, reduced vasodilation, and continued neutrophil activation. (
  • RESULTS There were significant differences in the amount of light scatter by the neutrophil populations in the symptomatic (p = 0.007) and severe asthmatic (p = 0.0001) groups compared with the control group. (
  • Several immunocompromised patient populations demonstrate BPI deficiency, including newborns, those with anti-neutrophil cytoplasmic antibodies (as in cystic fibrosis and HIV infection) and those exposed to radiochemotherapy. (
  • During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators - stored in granules - as well as in de novo synthesis of various mediators like cytokines and chemokines. (
  • The neutrophil is a central cellular effector of the innate immune system whose importance to host defense is manifest in the increased frequency and severity of infections in patients who have defects in neutrophil quantity or quality. (