21 Lohmannr Matthes ML, Steinmller C, Franker Ullmann G. Pulmonary macrophages. Eur Respir J, 1994,7:16781689.
17 Paterson DJ, Jefferies WA, Broanson M, et al. Antigens of activated Rat T Lymphocytes including a molecule of 50,000 Mr, detected only on CD4 positive T blasts. Mol Immunol, 1987,24:12811290.
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neutrophils (PMN) derived from bone marrow, as the final differentiation of cells, distributed in peripheral tissue and circulating pool, its life expectancy is shorter, but infection and immune response in the micro-environment can significantly extend their life. As PMN and EOS play in acute asthma when they are activated switch, it can increase the EOS in the characteristic changes in asthma [26], research has shown that asthma and asthma exacerbated by the continuing state of PMN in BALF and sputum or increase in the number is close related. ENFUMOSA (Mechanisms of Severe Asthma European Network) study, PMN not only can lead to acute deterioration of asthma, there is also a large number of patients in chronic severe asthma, airway, the number of nocturnal asthma attack and the PMN. In a number of sudden deaths due to asthma autopsy found that his sputum dominate the PMN, rather than the EOS [27]. This shows that the PMN airway inflammation in asthma, played an important role. In recent years, domestic scholars have found that in sudden fatal asthma, status asthmaticus, and glucocorticoid therapy in asthma, PMN-induced airway inflammation plays a decisive role [28]. Zhu et al [29] have confirmed that IL8 is a strong activation of PMN cytokine, which by increasing cytoplasmic free calcium concentration in a temporary increase to the activation of PMN. Also found that in addition to activation of IL8 PMN, but also to promote PMN upward flow within the respiratory tract. Activated PMN release of enzymes, chemotactic agents, antispasmodic agents cause a variety of inflammatory mediators and cytokines, including MPO, NE, matrix metalloproteinase (MMP), IL1α, IL8, TNFα, free radicals, leukotrienes, platelet-activating factors, NO, etc. [30], specifically, PMN may be involved in the mechanism of asthma in the following aspects: (1) protease tissue damage, PMN particle includes 20 kinds of enzymes, including elastase, collagenase and gelatin enzymes proteolytic enzymes are most effective when tissue damage. They can break down the immune globulin, complement proteins and other extracellular matrix, thereby undermining the organization normal structure. (2) oxygen metabolites on tissue injury, PMN exist nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase, to generate O2, H2O2, HOX (X = Cl, Br, I, SCN) causes tissue damage, particularly among the most important role of HOCl. (3) the biological effects of tissue hormones, PMN can synthesize a variety of arachidonic acid metabolites, the more important is the PG and LTB, they chemotaxis of inflammatory cells and cause vasodilation and increased permeability; In addition, PMN source living things can promote histamine release histamine and serotonin (5HT) release and can lead to bronchospasm. PMN also through the release of PAF, TNFa, IL8 and other inflammatory cells produce a wide range of other biological effects.
2 DeMonchy JG, Kauffman HF, Venge P, et al. Bronchoalveolar eosinophils during allergeninduced late asthmatic reaction.Am Rev Respir DIS, 1985,131:373.
4 Metzger WJ, Zavala D, Richerson HB. Local allergen challenge and bronchoalveolar lavage of allergic asthmatic lungs.descrioition of local airway inflammation. Am Rev Respir Dis, 1987,135:433.
body macrophages are the most important one of immune effector and phagocytic cells, specially phagocytic destruction of invading pathogens, foreign bodies, apoptotic cells and metabolites, chemotaxis, phagocytosis and induction of immune responses in the boot process plays a key role in linking [20]. Alveolar macrophages (AMS) is normal and airway inflammation in patients with lower respiratory tract is one of the main cell, there are studies that AMs are an important regulator of airway inflammation cells, through private placement and activation of inflammatory cells to produce inflammatory mediators , synthesis and release control and regulation of airway inflammation cytokines involved in airway inflammatory process. Airway inflammation in AMs of two sources, in addition to alveolar and distal bronchial inherent, there is also in part by migration from peripheral blood monocytes / macrophages.
peripheral blood basophils accounted for a small part, because the cytoplasm contains basophilic granules named, since these cells and mast cells are similar, so often that basophils may be immature, uncalled for, cycle of mast cells. It comes from the umbilical cord blood, peripheral blood and bone marrow CD34 precursor cells, in particular that from the CD34 / IL3R2 / IL5 eosinophils / basophils evolved precursor cells, and mast cells, basophils neutrophil cell surface with specific antigen, in certain conditions, can release a large number of regulatory factors, some of these regulatory factors in mast cells and basophils in common, we all know, in basophils in allergic plays the role of primary effector cells, which is activated after the release of histamine and cytokines and other inflammatory mediators involved in the occurrence and development of allergy [23]. It can store and release large amounts of histamine, causing bronchoconstriction, bronchial blood flow, increased vascular permeability, and promote mucus secretion, but also as an eosinophil chemotactic agent. Recent studies have found that the surface of basophils along with the CD40 ligand, CCR3 and CD63 expression [24], cells release large amounts of cytokines IL3, IL4, IL5, these cytokines can up-regulate adhesion molecules and release of inflammatory mediators . Traditional knowledge, dependent on allergen-mediated cross-linking FcεRI and, basophils in IgE-mediated allergy in the work. And after IgE receptor crosslinking, basophils regulator is more complex interconnected network of second messengers triggered release. Research has shown that: trypsin, anti-IgE antibody, CI, FM LP, C5a and substance P can induce significant basophils to release histamine, heparin can increase substance P and C5a-induced basophil histamine release with zoom neutrophil activation signals [25]. Is clear is that basophils by secreting inflammatory mediators and increased inflammation in the delayed phase of allergic play an important role in the release of inflammatory mediators and their receptor binding of IgE level and not necessarily linked, but it is by an endogenous biochemical mechanisms of control, this mechanism has been some genetic factors may be regulated, in short, so far, the activation of basophils in the pathogenesis of asthma is the specific mechanism of action also further study.
9 Metcalfe DD, Baram D, Mekori YA. Mast cell. Physiol Rev, 1997,77:10331079.
24 Sanz ML, Gamboa PM, Antepara I, et al. Flow cytometric basophil activation test by detection of CD63 expression in patients with immediatetype reactions to betalactam antibiotics.Clin Exp Allergy, 2002,32:277286.
13 Kummer F. Immunopathology and immunotherapy. New York: Springverla Wien, 1993.26.
T lymphocytes is body of important immune cells, which secrete cytokines and chemokines involved in the start of airway inflammation and enlarged it in asthma play a key regulatory role, T-cell activation by allergen release IL5, IL3 and granulocyte monocyte colony-stimulating factor (GMCSF) and other pro-inflammatory cytokines, these cytokines and chemokines can regulate airway inflammation and development, specifically the recruitment and activation of EOS caused by the release of inflammatory mediators of airway injury mucosa, causing smooth muscle spasm, induced airway remodeling. In recent years, found that T cells, especially Th-cell dysfunction in asthma plays an important role [12,13]. Cytokine production by T helper lymphocytes from the different functions will be divided into two subsets Th1 and Th2 [14], the former mainly produce IL2, IFNγ; which mainly produce IL4, IL5, IL6, IL10, both under normal circumstances reaches a certain balance, once the imbalance will lead to certain diseases. Foreign scholars have found the experiment after injection of OVA, mice can produce typical Th2 cell immune response [15]. Reported in the literature, inhibition of Th2 cell responses in experimental asthma in mice reduces airway inflammation. Th2 cells secrete IL4, IL5 can promote asthma and other airway EOS infiltration in mice and prolong their survival time, thereby increasing the area of ??inflammatory injury, and the application of Th1-type cytokines, such as (IFNγ), when the inflammatory response of asthma have more good control effect. Some scholars have confirmed the existence of T cell activation in patients with asthma, especially CD4 Th2 activation and abnormal secretion of inflammatory cytokines involved in the formation of asthma [16]. IL2R surface of T cell activation is one of the signs, mainly expressed in CD4 T cells [17], sustained activation of its abnormal secretion of inflammatory cytokines and thus an essential component. Costimulatory role of lymphocyte activation has a crucial importance. T cell activation requires two different types of signals. The first signal from the T-cell receptor and antigen-presenting cells (APC), surface type major histocompatibility complex molecules on antigen complex interaction exists; second signal for T cell surface molecules CD28 and APC surface interaction of B7 molecules to T cells after passing the so-called co-stimulatory signals. CD40 / CD 40L is a pair of second outside than B7/CD28 costimulatory pathway in the sensitization and airway inflammation plays an important role in all stages of effects, its presence can increase the expression of B7/CD28 in [18, 19 ]. These show that asthma may be an increased activity of the Th2 type of immune response cell disease, since the immune response, there must be CD40 / CD 40L participation of costimulatory molecules, activation of cells, which will eventually lead to Th2 type cells produce a series of cytokines, promote the production of IgE, chronic airway inflammation.
allergic bronchial asthma as an inflammatory disease, the process involved in the pathogenesis of acute hypersensitivity and delayed-type hypersensitivity to, in their different reaction phase, a variety of effector cells involved. These effector cells with inflammatory cells and cells of complex signal transduction system to transmit information, the formation of asthmatic patients in vivo by the cytokines, adhesion molecules, inflammatory mediators and other components of the complex network, which through the release of cytokines, inflammatory mediators the start of the inflammation, development and regulation play an important role.
6 Matsumoto K, Saito H. The role of eosinophils in asthma; Sarastro or the Queen of Night? Int Arch Allergy Immunol, 2001,125:240246.
3 lymphocytes
18 Crewal IS , Flavell RA. A central role of CD40 ligand in the regulation of CD 4 Tcell responses. Immunol Today, 1996,17:410414.
8 Xie, HE Shao-heng, specific inhibitor of tryptase double Benzamidine the role of mast cells in vitro. Cellular and Molecular Immunology, 2003,1:100102.
allergy plays as the primary effector cells of the mast cells from CD34 bone marrow progenitor cells, mainly mediated by type Ⅰ hypersensitivity, which are widely distributed in the body, more allergens into the body at the entrance area, He et al [7,8] found that protease activated receptor-2 in mast cell activation, and its secretion by activated tryptase By re-activating its protease on the cell membrane PAR2 form of self-amplification mechanism of cell activation. Mast cells are activated after the release of histamine and cytokines, proteases that proteoglycans and other allergic inflammatory mediators involved in the occurrence and development. It is usually located in the lung bronchial and alveolar walls of the epidermis, or separated from the bronchial lumen, so in these parts, the inhalation of allergens can be easily and high-affinity IgE receptor-specific IgE on combination of a series of inflammatory mediators and induce bronchoconstriction substance release. Studies have also found their participation in many chronic inflammatory diseases, such as wound healing, fibrosis and innate immunity [9]. In the late allergic reaction can be observed in the bronchial mucosa to increase the number of mast cells [10]; In addition, in inflammation and fibrosis of repair and reconstruction phase can be detected mast cell hyperplasia [11]. Mast cell-associated proteases including the stomach and promote trypsin and tryptase are able to degrade a variety of extracellular peptides and proteins, including vasoactive intestinal peptide, neuropeptide bronchiectasis. In addition, tryptase to inactivate procoagulant protein, inhibition of fibrin deposition, activation of urokinase, which can promote the dissolution of fibrin. In this way, tryptase can promote white blood cells into inflamed tissue. Tryptase via activation of matrix metalloproteinases and stimulate fibroblasts and airway smooth muscle cell growth, in the process of airway remodeling in asthma caused to the key role. Thus we can conclude that mast cell-related protease is induced by the process of airway remodeling in asthma an important medium.
26 Hoshino M, Takahashi M, Aoike N. Expression of vascular endothelial growth factor, basic fibroblast growth factor, and angiogenin immunoreactivity in asthmatic airways and its relationship to angiogenesis. Allergy Clin Immunol, 2001,107:295301.
3 Durham SR, Kay AB. Eosinophils, bronchial hyperreactivity and late asthmatic reaction. Clin Allergy, 1985,15:411.
15 Hsieh CS, Macatonia SE, OGarra A, et al. T cell genetic background determines default helper phenotype development in vitro.J Exp Med, 1995, 181:713721.
16 Willian WB, Robert LC, Coffman EW. Mechanisms of persistent airway inflammati on in asthma: A role for T cells and T cell products. Am J Respir Crit Care Med, 1995, 152:388393.
【Keywords】 asthma; effector cells
22 Zetterberg G, Elmberger G, Johansson A, et al. Ratalveolar and interstitial macrophages in the fibrosing stage following quartz exposure. Hum ExpToxicol, 2000,19:402411.
11 Piliponsky AM, LevrSchaffer F. Regulation of apoptosis in mast cells. Apoptosis, 2000,5:435441.
allergic asthma, the main effect of airway cells were eosinophils (EOS), which can produce a variety of cytokines and inflammatory mediators, causing an amicable Road lesions hyperresponsiveness, the release of oxidation products can damage lung tissue surrounding the integrity. EOS by releasing a series of important inflammatory neurotransmitters, promoting monocytes, lymphocytes and EOS itself raised. EOS is an increase in atopic diseases (atopicdisease) a common feature, marked by the generation of EOS in the bone marrow selectively increase the number of peripheral blood EOS and EOS in the effects of elevated parts of the aggregation. EOS in the bone marrow produce, are granulocyte cell lines, the EOS in the bone marrow progenitor cells in IL3, IL5, GMCSF differentiate into mature under the influence of the EOS, migrate through the blood circulation to the airway. EOS raised in the lungs and the release of inflammatory mediators, airway inflammation is one of the key, asthma, peripheral blood, sputum, bronchoalveolar lavage fluid (BALF) and airway biopsies were significantly increased the number of EOS. EOS activation by the cellular signal transduction mechanisms of control, main ways: RASRAFMAPK signal transduction pathways, SAKSTAT way to the PI3K pathway and the NFκB pathway [1]. Endothelial activation is captured by the EOS, raised around the airway inflammation, the occurrence of functional and phenotypic changes, resulting in local tissue release of inflammatory mediators, can produce IL3, IL5, IL6, TGFα, TGFβ, TNFΑ other cells factor, in order to maintain their way of development of inflammation. More and more experimental evidence, EOS as effector cells in bronchial asthma, especially in late-phase asthmatic reactions play a very important role [2,3].
1 Wong C, Zhang J, Ip WK, et al.Intracellular signal transduction in eosinophils and its clinical significance.Immunopharmacol Immunotoxicol, 2002,24:165186. Review.
EOS activation and release of granule protein Asthma is caused by pathological changes characteristic of late-phase airway hyperresponsiveness main reason for these EOS granule proteins include basic protein (MBP), EOS cationic protein (ECP), EOS peroxidase (EPO), and EOS neurotoxin (EDN). Research has shown that accumulation of EOS products, such as MBP, ECP, and EDN in allergen-induced late-phase reaction found in the BALF [4], and increased AHR and the number of their products is closely related to the EOS [5]. In these proteins MBP toxicity was particularly notable, into the MBP to lung tissue, airway hyperresponsiveness was significantly increased, induced bronchospasm; activation of neutrophils and alveolar macrophages, and promote mast cell and basophil release histamine; destruction of membrane lipid bilayer, changes in tissue enzyme activity, causing cell damage, airway epithelial shedding. It is worth mentioning is the EOS granule protein and also airway remodeling of asthma relationship, Matsumoto et al [6] is confirmed by the study of airway remodeling in MBP also have an important impact, which can be a conclusion, EOS in bronchial asthma development is at the core of the effector cells, so some scholars will also be represented by asthma chronic airway inflammation (allergic airway inflammation) called EOS inflammation.
5 Lam S, LeRiche J, Phillips D, et al.Celluar and protein changes in bronchial lavage fluid after late asthmatic reaction in patients with red cedar asthma. Allergy Clin Immunol, 1987,80:40.
29 Zhu Z, Lee CG, Zheng T, et al. Airway inflammation and remodeling in asthma. Lessons from interleukin 11 and interleukin 13 transgenic mice. Am Respir Crit Care Med, 2001,164:6770.
AMs with other body as part of the mononuclear cells with strong heterogeneity, this heterogeneity is likely derived from bone marrow mononuclear cells from the previous release, which originated from different precursor cells. It has been confirmed in the respiratory tract have different immune functions of alveolar macrophages from different subsets of bone marrow precursor cells. AMs in morphology, density, and phenotypic heterogeneity on the decision of its immune response in the airway inflammation of different functions. Alveolar macrophages of the two largest sub-group of the AM and IM. AM in the airways and alveoli, is non-specific respiratory response to the first line of defense that can effectively dissolve, eating poorly water-soluble organic particles, the release of inflammatory mediators, antigen presentation, expression of different membrane receptors, are important microbicidal effector cells [21]. IM in the pulmonary interstitial, in part play a role in immune defense, is an important regulator of immune cell function [22]. In general, AMs are the body vital immune cells, it is a huge amount of widely distributed, easily access antigens at the same time, AMs expressing MHC Ⅱ antigen can be processed after the delivery of foreign antigens presented to Th2 cells. AMs release of LTB4, PAF and so on eosinophils, lymphocytes, neutrophils have a strong chemotactic effect, leading these cells to the airway raised, starting late-phase asthmatic reactions. AMs release of chemokines, inflammatory mediators can cause airway mucosal injury, microvascular leakage, mucus secretion causes airway hyperresponsiveness and airway remodeling.
28 Lin Jian, Wu Rongxi, Li Changchong. neutrophils in the pathogenesis of bronchial asthma in the role. International Journal of Pediatrics Volume, 2001,28:2224.
2 mast cell
10 Crimi E, Chiaramondia M, Milanese M, et al.Increased numbers of mast cells in bronchial mucosa after the late phase asthmatic response to allergen.Am Rev Respir Dis, 1991,144:12821286.
6 neutrophils < br /> 23 Wedemeyer J, Tsai M, Galli SJ. Roles of mast cells and basophils in innate and acquird immunity. Curr Opin Immunol, 2000,12:624631.
In summary, asthma is a multi types of effector cells involved in complex chronic airway inflammatory disease, these effector cells in the inflammatory response during cross-linking, interdependence, regulates the development of inflammation, joint decision of the airway inflammation in morphology, tissue , molecular biological characteristics. No do not doubt that, with the application of new technologies of molecular biology and molecular genetics of development, the study of bronchial asthma will be further in-depth, effects of these inflammatory cells to airway inflammation pathways and mechanisms will also be more clearly .
30 Dahlen B, Shute J, Howarth [Popular] credit card no annual fee for life can be? bank credit card is somewhat non-permissive _ News P. Immunohistochemical localization of the Matrix metalloproteinases MMP3 and MMP9 within the airways in asthma. Thorax, 1999,54:590596.
27 Sur S, Crotty TB, Kephart GM, et al. Suddenonset fatal asthma.Adistinct entity with few eosinophils and relatively more neutrophils in the airway submucosa? Am Rev Respir Dis, 1993,148: 713719.
25 Zhu Wei, HE Shao-Heng, Xia Hayashi, etc. in different human basophils under the action of stimuli ability to release histamine. Cellular and Molecular Immunology, 2005,21:519521.
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19 Nagafuchi H, Shimoyama Y, Kashiwakura J, et al. Preferential expression of B7. 2 (CD86), but not B7.1 (CD80), on B cells induced by CD40/CD40L inter action is essential for antiDNA autoantibody production in patients with system is lupus erythematosus. Clin Exp Rheumatol, 2003,21:7177.
Carl Articles Articles to write on behalf of the fat Tel: 18971222098 work QQ: 27997038 E-mail: kr.27 @ qq.com
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20 Lei, WANG Zheng, Hu Cheng Hong, etc. Trauma abnormal serum protein on macrophage function of the study of Chinese Critical Care Medicine, 1998,10:494496.
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