White blood cell
White blood cells are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from multipotent cells in the bone marrow known as hematopoietic stem cells. Leukocytes are found throughout the body, including lymphatic system. All white blood cells have nuclei, which distinguishes them from the other blood cells, the anucleated red blood cells and platelets. Types of white blood cells can be classified in standard ways. Two pairs of broadest categories classify them either by cell lineage; these broadest categories can be further divided into the five main types: neutrophils, basophils and monocytes. These types are distinguished by their physical and functional characteristics. Monocytes and neutrophils are phagocytic. Further subtypes can be classified; the number of leukocytes in the blood is an indicator of disease, thus the white blood cell count is an important subset of the complete blood count.
The normal white cell count is between 4 × 109/L and 1.1 × 1010/L. In the US, this is expressed as 4,000 to 11,000 white blood cells per microliter of blood. White blood cells make up 1% of the total blood volume in a healthy adult, making them less numerous than the red blood cells at 40% to 45%. However, this 1 % of the blood makes a large difference to health. An increase in the number of leukocytes over the upper limits is called leukocytosis, it is normal. It is abnormal, when it is neoplastic or autoimmune in origin. A decrease below the lower limit is called leukopenia; this indicates a weakened immune system. The name "white blood cell" derives from the physical appearance of a blood sample after centrifugation. White cells are found in the buffy coat, a thin white layer of nucleated cells between the sedimented red blood cells and the blood plasma; the scientific term leukocyte directly reflects its description. It is derived from the Greek roots leuk- meaning "white" and cyt- meaning "cell".
The buffy coat may sometimes be green if there are large amounts of neutrophils in the sample, due to the heme-containing enzyme myeloperoxidase that they produce. All white blood cells are nucleated, which distinguishes them from the anucleated red blood cells and platelets. Types of leukocytes can be classified in standard ways. Two pairs of broadest categories classify them either by cell lineage; these broadest categories can be further divided into the five main types: neutrophils, basophils and monocytes. These types are distinguished by their physical and functional characteristics. Monocytes and neutrophils are phagocytic. Further subtypes can be classified. Granulocytes are distinguished from agranulocytes by their nucleus shape and by their cytoplasm granules; the other dichotomy is by lineage: Myeloid cells are distinguished from lymphoid cells by hematopoietic lineage. Lymphocytes can be further classified as T cells, B cells, natural killer cells. Neutrophils are the most abundant white blood cell, constituting 60-70% of the circulating leukocytes, including two functionally unequal subpopulations: neutrophil-killers and neutrophil-cagers.
They defend against fungal infection. They are first responders to microbial infection, they are referred to as polymorphonuclear leukocytes, although, in the technical sense, PMN refers to all granulocytes. They have a multi-lobed nucleus; this gives the neutrophils the appearance of having multiple nuclei, hence the name polymorphonuclear leukocyte. The cytoplasm may look transparent because of fine granules. Neutrophils are active in phagocytosing bacteria and are present in large amount in the pus of wounds; these cells are not able to die after having phagocytosed a few pathogens. Neutrophils are the most common cell type seen in the early stages of acute inflammation; the life span of a circulating human neutrophil is about 5.4 days. Eosinophils compose about 2-4% of the WBC total; this count fluctuates throughout the day and during menstruation. It rises in response to allergies, parasitic infections, collagen diseases, disease of the spleen and central nervous system, they are rare in the blood, but numerous in the mucous membranes of the respiratory and lower urinary tracts.
They deal with parasitic infections. Eosinophils are the predominant inflammatory cells in allergic reactions; the most important causes of eosinophilia include allergies such as asthma, hay fever, hives. They secrete chemicals that destroy these large parasites, such as hook worms and tapeworms, that are too big for any one WBC to phagocytize. In general, their nucleus is bi-lobed; the lobes are connected by a thin strand. The cytoplasm is full of granules that assume a characteristic pink-orange color with eosin stain
Human serum albumin
Human serum albumin is the serum albumin found in human blood. It is the most abundant protein in human blood plasma, it is produced in the liver. It is soluble in monomeric. Albumin transports hormones, fatty acids, other compounds, buffers pH, maintains oncotic pressure, among other functions. Albumin is synthesized in the liver as preproalbumin, which has an N-terminal peptide, removed before the nascent protein is released from the rough endoplasmic reticulum; the product, proalbumin, is in turn cleaved in the Golgi vesicles to produce the secreted albumin. The reference range for albumin concentrations in serum is 35–50 g/L, it has a serum half-life of 20 days. It has a molecular mass of 66.5 kDa. The gene for albumin is located on chromosome 4 in locus 4q13.3 and mutations in this gene can result in anomalous proteins. The human albumin gene is 16,961 nucleotides long from the putative'cap' site to the first poly addition site, it is split into 15 exons that are symmetrically placed within the 3 domains thought to have arisen by triplication of a single primordial domain.
Maintains oncotic pressure Transports thyroid hormones Transports other hormones, in particular, ones that are fat-soluble Transports fatty acids to the liver and to myocytes for utilization of energy Transports unconjugated bilirubin Transports many drugs. As such, it is not a valid marker of nutritional status. Serum albumin concentration is 35–50 g/L. Hypoalbuminemia means low blood albumin levels; this can be caused by: Liver disease. This condition is due to dehydration. Hyperalbuminemia has been associated with high protein diets. Human albumin solution or HSA is available for medical use at concentrations of 5–25%. Human albumin is used to replace lost fluid and help restore blood volume in trauma and surgery patients. A Cochrane systematic review of 37 trials found no evidence that albumin, compared with cheaper alternatives such as saline, reduces the risk of dying. Human serum albumin has been used as a component of a frailty index, it has not been shown to give better results than other fluids when used to replace volume, but is used in conditions where loss of albumin is a major problem, such as liver disease with ascites.
It has been known for a long time that human blood proteins like hemoglobin and serum albumin may undergo a slow non-enzymatic glycation by formation of a Schiff base between ε-amino groups of lysine residues and glucose molecules in blood. This reaction can be inhibited in the presence of antioxidant agents. Although this reaction may happen elevated glycoalbumin is observed in diabetes mellitus. Glycation has the potential to alter the biological structure and function of the serum albumin protein. Moreover, the glycation can result in the formation of Advanced Glycation End-Products, which result in abnormal biological effects. Accumulation of AGEs leads to tissue damage via alteration of the structures and functions of tissue proteins, stimulation of cellular responses, through receptors specific for AGE-proteins, generation of reactive oxygen intermediates. AGEs react with DNA, thus causing mutations and DNA transposition. Thermal processing of proteins and carbohydrates brings major changes in allergenicity.
AGEs represent many of the important neoantigens found in cooked or stored foods. They interfere with the normal product of nitric oxide in cells. Although there are several lysine and arginine residues in the serum albumin structure few of them can take part in the glycation reaction, it is not clear why only these residues are glycated in serum albumin, but it is suggested that non-covalent binding of glucose to serum albumin prior to the covalent bond formation might be the reason. The albumin is the predominant protein in most body fluids, its Cys34 represents the largest fraction of free thiols within body; the albumin Cys34 thiol exists in both oxidized forms. In plasma of healthy young adults, 70–80% of total HSA contains the free sulfhydryl group of Cys34 in a reduced form or mercaptoalbumin. However, in pathological states characterized by oxidative stress and during the aging process, the oxidized form, or non-mercaptoalbumin, could predominate; the albumin thiol reacts with radical hydroxyl, hydrogen peroxide and the reactive nitrogen species as peroxynitrite, have been shown to oxidize Cys34 to sulfenic acid derivate, it can be recycled to mercapto-albumin.
Red blood cell
Red blood cells known as RBCs, red cells, red blood corpuscles, erythroid cells or erythrocytes, are the most common type of blood cell and the vertebrate's principal means of delivering oxygen to the body tissues—via blood flow through the circulatory system. RBCs take up oxygen in the lungs, or gills of fish, release it into tissues while squeezing through the body's capillaries; the cytoplasm of erythrocytes is rich in hemoglobin, an iron-containing biomolecule that can bind oxygen and is responsible for the red color of the cells and the blood. The cell membrane is composed of proteins and lipids, this structure provides properties essential for physiological cell function such as deformability and stability while traversing the circulatory system and the capillary network. In humans, mature red blood cells are oval biconcave disks, they lack most organelles, in order to accommodate maximum space for hemoglobin. 2.4 million new erythrocytes are produced per second in human adults. The cells develop in the bone marrow and circulate for about 100–120 days in the body before their components are recycled by macrophages.
Each circulation takes about 60 seconds. A quarter of the cells in the human body are red blood cells. Nearly half of the blood's volume is red blood cells. Packed red blood cells are red blood cells that have been donated and stored in a blood bank for blood transfusion. All vertebrates, including all mammals and humans, have red blood cells. Red blood cells are cells present in blood; the only known vertebrates without red blood cells are the crocodile icefish. While they no longer use hemoglobin, remnants of hemoglobin genes can be found in their genome. Vertebrate red blood cells consist of hemoglobin, a complex metalloprotein containing heme groups whose iron atoms temporarily bind to oxygen molecules in the lungs or gills and release them throughout the body. Oxygen can diffuse through the red blood cell's cell membrane. Hemoglobin in the red blood cells carries some of the waste product carbon dioxide back from the tissues. Myoglobin, a compound related to hemoglobin, acts to store oxygen in muscle cells.
The color of red blood cells is due to the heme group of hemoglobin. The blood plasma alone is straw-colored, but the red blood cells change color depending on the state of the hemoglobin: when combined with oxygen the resulting oxyhemoglobin is scarlet, when oxygen has been released the resulting deoxyhemoglobin is of a dark red burgundy color. However, blood can appear bluish when seen through skin. Pulse oximetry takes advantage of the hemoglobin color change to directly measure the arterial blood oxygen saturation using colorimetric techniques. Hemoglobin has a high affinity for carbon monoxide, forming carboxyhemoglobin, a bright red in color. Flushed, confused patients with a saturation reading of 100% on pulse oximetry are sometimes found to be suffering from carbon monoxide poisoning. Having oxygen-carrying proteins inside specialized cells was an important step in the evolution of vertebrates as it allows for less viscous blood, higher concentrations of oxygen, better diffusion of oxygen from the blood to the tissues.
The size of red blood cells varies among vertebrate species. The red blood cells of mammals are shaped as biconcave disks: flattened and depressed in the center, with a dumbbell-shaped cross section, a torus-shaped rim on the edge of the disk; this shape allows for a high surface-area-to-volume ratio to facilitate diffusion of gases. However, there are some exceptions concerning shape in the artiodactyl order, which displays a wide variety of bizarre red blood cell morphologies: small and ovaloid cells in llamas and camels, tiny spherical cells in mouse deer, cells which assume fusiform, lanceolate and irregularly polygonal and other angular forms in red deer and wapiti. Members of this order have evolved a mode of red blood cell development different from the mammalian norm. Overall, mammalian red blood cells are remarkably flexible and deformable so as to squeeze through tiny capillaries, as well as to maximize their apposing surface by assuming a cigar shape, where they efficiently release their oxygen load.
Red blood cells in mammals are unique amongst vertebrates. Red blood cells of mammals cells have nuclei during early phases of erythropoiesis, but extrude them during development as they mature; the red blood cells without nuclei, called reticulocytes, subsequently lose all other cellular organelles such as their mitochondria, Golgi apparatus and endoplasmic reticulum. The spleen acts as a reservoir of red blood cells. In some other mammals such as dogs and horses, the spl
Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in all mammals. It is distantly related to hemoglobin, the iron- and oxygen-binding protein in blood in the red blood cells. In humans, myoglobin is only found in the bloodstream after muscle injury, it is an abnormal finding, can be diagnostically relevant when found in blood. Myoglobin is the primary oxygen-carrying pigment of muscle tissues. High concentrations of myoglobin in muscle cells allow organisms to hold their breath for a longer period of time. Diving mammals such as whales and seals have muscles with high abundance of myoglobin. Myoglobin is found in Type I muscle, Type II A and Type II B, but most texts consider myoglobin not to be found in smooth muscle. Myoglobin was the first protein to have its three-dimensional structure revealed by X-ray crystallography; this achievement was reported in 1958 by associates. For this discovery, John Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz.
Despite being one of the most studied proteins in biology, its physiological function is not yet conclusively established: mice genetically engineered to lack myoglobin can be viable and fertile but show many cellular and physiological adaptations to overcome the loss. Through observing these changes in myoglobin-deplete mice, it is hypothesised that myoglobin function relates to increased oxygen transport to muscle, oxygen storage and as a scavenger of reactive oxygen species. In humans myoglobin is encoded by the MB gene. Myoglobin can take the forms oxymyoglobin and metmyoglobin, analogously to hemoglobin taking the forms oxyhemoglobin, carboxyhemoglobin, methemoglobin. Like hemoglobin, myoglobin is a cytoplasmic protein, it harbors only one heme group. Although its heme group is identical to those in Hb, Mb has a higher affinity for oxygen than does hemoglobin; this difference is related to its different role: whereas hemoglobin transports oxygen, myoglobin's function is to store oxygen. Myoglobin contains hemes, pigments responsible for the colour of red meat.
The colour that meat takes is determined by the degree of oxidation of the myoglobin. In fresh meat the iron atom is in the ferrous oxidation state bound to an oxygen molecule. Meat cooked well done is brown because the iron atom is now in the ferric oxidation state, having lost an electron. If meat has been exposed to nitrites, it will remain pink because the iron atom is bound to NO, nitric oxide. Grilled meats can take on a pink "smoke ring" that comes from the iron binding to a molecule of carbon monoxide. Raw meat packed in a carbon monoxide atmosphere shows this same pink "smoke ring" due to the same principles. Notably, the surface of this raw meat displays the pink color, associated in consumers' minds with fresh meat; this artificially induced pink color can persist up to one year. Hormel and Cargill are both reported to use this meat-packing process, meat treated this way has been in the consumer market since 2003. Myoglobin is released from damaged muscle tissue, which has high concentrations of myoglobin.
The released myoglobin is filtered by the kidneys but is toxic to the renal tubular epithelium and so may cause acute kidney injury. It is not the myoglobin itself, toxic but the ferrihemate portion, dissociated from myoglobin in acidic environments. Myoglobin is a sensitive marker for muscle injury, making it a potential marker for heart attack in patients with chest pain. However, elevated myoglobin has low specificity for acute myocardial infarction and thus CK-MB, cardiac Troponin, ECG, clinical signs should be taken into account to make the diagnosis. Myoglobin belongs to the globin superfamily of proteins, as with other globins, consists of eight alpha helices connected by loops. Myoglobin contains 154 amino acids. Myoglobin contains a porphyrin ring with an iron at its center. A proximal histidine group is attached directly to iron, a distal histidine group hovers near the opposite face; the distal imidazole is not bonded to the iron but is available to interact with the substrate O2. This interaction encourages the binding of O2, but not carbon monoxide, which still binds about 240× more than O2.
The binding of O2 causes substantial structural change at the Fe center, which shrinks in radius and moves into the center of N4 pocket. O2-binding induces "spin-pairing": the five-coordinate ferrous deoxy form is high spin and the six coordinate oxy form is low spin and diamagnetic. Many models of myoglobin have been synthesized as part of a broad interest in transition metal dioxygen complexes. A well known example is the picket fence porphyrin, which consists of a ferrous complex of a sterically bulky derivative of tetraphenylporphyrin. In the presence of an imidazole ligand, this ferrous complex reversibly binds O2; the O2 substrate adopts a bent geometry. A key property of this model is the slow formation of the μ-oxo dimer, an inactive diferric state. In nature, such deactivation pathways are suppressed by protein matrix that prevents close approach of the Fe-porphyrin assemblies. Cytoglobin Hemoglobin Hemoprotein Neuroglobin Phytoglobin Myoglobinuria - The presence of myoglobin in the urine Ischemia-reperfusion injury of the appendicular musculoskeletal system Online Mendelian Inheritance in Man 160000 human genetics The Myoglobin Protein Protein Database featured mole
Eosinophils, sometimes called eosinophiles or, less acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along with mast cells and basophils, they control mechanisms associated with allergy and asthma, they are granulocytes that develop during hematopoiesis in the bone marrow before migrating into blood, after which they are terminally differentiated and do not multiply. These cells are eosinophilic or "acid-loving" due to their large acidophilic cytoplasmic granules, which show their affinity for acids by their affinity to coal tar dyes: Normally transparent, it is this affinity that causes them to appear brick-red after staining with eosin, a red dye, using the Romanowsky method; the staining is concentrated in small granules within the cellular cytoplasm, which contain many chemical mediators, such as eosinophil peroxidase, deoxyribonucleases, lipase and major basic protein.
These mediators are released by a process called degranulation following activation of the eosinophil, are toxic to both parasite and host tissues. In normal individuals, eosinophils make up about 1–3% of white blood cells, are about 12–17 micrometres in size with bilobed nuclei. While they are released into the bloodstream as neutrophils are, eosinophils reside in tissue, they are found in the medulla and the junction between the cortex and medulla of the thymus, and, in the lower gastrointestinal tract, uterus and lymph nodes, but not in the lungs, esophagus, or some other internal organs under normal conditions. The presence of eosinophils in these latter organs is associated with disease. For instance, patients with eosinophilic asthma have high levels of eosinophils that lead to inflammation and tissue damage, making it more difficult for patients to breathe. Eosinophils persist in the circulation for 8–12 hours, can survive in tissue for an additional 8–12 days in the absence of stimulation.
Pioneering work in the 1980s elucidated that eosinophils were unique granulocytes, having the capacity to survive for extended periods of time after their maturation as demonstrated by ex-vivo culture experiments. TH2 and ILC2 cells both express the transcription factor GATA-3 which promotes the production of TH2 cytokines, including the interleukins. IL-5 controls the development of eosinophils in the bone marrow, as they differentiate from myeloid precursor cells, their lineage fate is determined by transcription factors, including GATA and C/EBP. Eosinophils produce and store many secondary granule proteins prior to their exit from the bone marrow. After maturation, eosinophils circulate in blood and migrate to inflammatory sites in tissues, or to sites of helminth infection in response to chemokines like CCL11, CCL24, CCL5, 5-hydroxyicosatetraenoic acid and 5-oxo-eicosatetraenoic acid, certain leukotrienes like leukotriene B4 and MCP1/4. Interleukin-13, another TH2 cytokine, primes eosinophilic exit from the bone marrow by lining vessel walls with adhesion molecules such as VCAM-1 and ICAM-1.
When eosinophils are activated, they undergo cytolysis, where the breaking of the cell releases eosinophilic granules found in extracellular DNA traps. High concentrations of these DNA traps are known to cause cellular damage, as the granules they contain are responsible for the ligand-induced secretion of eosinophilic toxins which cause structural damage. There is evidence to suggest that eosinophil granule protein expression is regulated by the non-coding RNA EGOT. Following activation, eosinophils effector functions include production of the following: Cationic granule proteins and their release by degranulation Reactive oxygen species such as hypobromite and peroxide Lipid mediators like the eicosanoids from the leukotriene and prostaglandin families Enzymes, such as elastase Growth factors such as TGF beta, VEGF, PDGF Cytokines such as IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-13, TNF alphaThere are eosinophils that play a role in fighting viral infections, evident from the abundance of RNases they contain within their granules, in fibrin removal during inflammation.
Eosinophils, along with basophils and mast cells, are important mediators of allergic responses and asthma pathogenesis and are associated with disease severity. They fight helminth colonization and may be elevated in the presence of certain parasites. Eosinophils are involved in many other biological processes, including postpubertal mammary gland development, oestrus cycling, allograft rejection and neoplasia, they have been implicated in antigen presentation to T cells. Eosinophils are responsible for tissue damage and inflammation including asthma. High levels of interleukin-5 has been observed to up regulate the expression of adhesion molecules, which facilitate the adhesion of eosinophils to endothelial cells, thereby causing inflammation and tissue damage. An accumulation of eosinophils in the nasal mucosa is considered a major diagnostic criterion for allergic rhinitis. Following activation by an immune stimulus, eosinophils degranulate to release an array of cytotoxic granule cationic proteins that are capable of inducing tissue damage and dysfunction.
These include: major basic protein eosinophil cationic protein eosinophil peroxidase eosinophil-derived neurotoxin Major basic protein, eosinophil peroxidase, eosinophil cationic protein are toxic to many tissues. Eosinophil cationic protein and eosinophil-derived neurotoxin are ribonucleases w
Eosinophil cationic protein
Eosinophil cationic protein known as ribonuclease 3 is a basic protein located in the eosinophil primary matrix. In humans, the eosinophil cationic protein is encoded by the RNASE3 gene. ECP is released during degranulation of eosinophils; this protein is related to inflammation and asthma because in these cases, there are increased levels of ECP in the body. There are three glycosolated forms of ECP and ECP has a range of molecular weights from 18-22 kDa. Eosinophil cationic protein and the sequence related eosinophil-derived neurotoxin are both members of the ribonuclease a superfamily. Both proteins possess neurotoxic, helmintho-toxic, ribonucleo-lytic activities. Eosinophil cationic protein is localized to the granule matrix of the eosinophil; the ribonuclease activity of ECP is not essential for cytotoxicity. When the two known ribonuclease active-site residues are modified to non-functional counterparts and compared to the wild-type ECP, the mutated ECP retains its cytotoxicity but no longer has its ribonuclease activity.
The experiment confirmed that converting the two amino acids to non-functional counterparts did inhibit ECP’s ribonuclease activity. However, ECP retained its anti-parasitic activity, it did not change the production and transportation of ECP in bacteria. ECP is a potent cytotoxic protein capable of killing cells of guinea pig tracheal epithelium, mammalian leukemia, epidermis carcinoma, breast carcinoma, as well as non-mammalian cells such as parasites and viruses. Mature ECP is cytotoxic to human bronchial epithelial cells by specific binding to cell surface heparan sulfate proteoglycans followed by endocytosis. Studies show that ECP, along with other RNases including EDN, had been reported to induce apoptosis in cells. A latest study indicated that ECP caused cytotoxicity in HL-60 and HeLa cells via caspase-3 like activity. Accordingly, cytotoxic RNases play an important role in cell death. However, the mechanism of ECP-induced apoptosis is still not verified. Recent studies have shown that eosinophils can induce epithelial cell death via apoptosis and necrosis.
ECP triggers apoptosis by caspase-8 activation through mitochondria-independent pathway. Increases in chromatin condensation, sub-G1 population, PARP cleavage, DNA fragmentation indicate that ECP induces apoptosis in human bronchial epithelial cells. Eosinophil granulocytes appear in large numbers in inflammation sites and in response to certain parasitic infections; these cytoplasmic granules contain positively charged proteins. ECP is one of the four basic proteins that enter the surrounding tissues when activated eosinophils degranulate. Although circulating ECP levels can vary among patients, some studies show that serum ECP measurements are useful in monitoring many active inflammatory diseases. ECP concentrations in plasma and other body fluids increase during inflammatory reactions marked by activated eosinophils. Serum ECP levels are a useful, objective measurement for asthma severity. Increased ECP levels correspond to symptom onset. In seasonal asthmatic patients, ECP measurement reflected changes in disease activity throughout the year.
There are several mechanisms that can be combined to generate an asthma attack, including specific IgE antibodies, activated inflammatory cells, neurogenic mechanisms, hyperresponsiveness and individual hormonal imbalances. Allergic reactions in the lung have two phases; the late phase occurs several hours after exposure, upon which eosinophils accumulate in the bronchus and release granule proteins that cause bronchial irritability. ECP is toxic to neurons, some epithelial cell lines, isolated myocardial cells; this could be a reason for itching disorders of the skin. Serum ECP concentrations have been linked to atopic dermatitis activity. ECP correlates with the symptoms for AD and correlates with the total clinical score. Serum ECP measurement for assessing asthma severity, monitoring therapy, indicating severity of certain inflammatory skin conditions present an advantage over subjective clinical measures that are prone to inconsistencies due to broad variability of individual investigator and patient assessments in young children.
The normal reference range for blood tests for eosinophil cationic protein is between 2.3 and 16 µg/L. Ribonuclease A Eosinophil+Cationic+Protein at the US National Library of Medicine Medical Subject Headings RNASE3+protein,+human at the US National Library of Medicine Medical Subject Headings