Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eosinophils represent one of the main effector cell populations of allergic airway inflammation and allergic bronchial asthma. Their infiltration correlates with many characteristics of the disease, including airway hyperresponsiveness (AHR) and increased mucus production. CCR-3 is the principle chemokine receptor involved in eosinophil attraction into inflamed tissue. Therefore, antagonizing CCR-3 could be a novel promising approach toward asthma therapy. We investigated the effect of a low-molecular-weight CCR-3 antagonist on established airway inflammation in a chronic model of experimental bronchial asthma. For this purpose, BALB/c mice intraperitoneally sensitized with ovalbumin (OVA) were chronically challenged with OVA aerosol to induce chronic airway inflammation and airway remodeling. The effect of antagonizing CCR-3 on asthma pathology was examined in BAL and lung histology. Airway reactivity was assessed by head-out body plethysmography. Treatment with the CCR-3 antagonist resulted in a marked reduction of eosinophils in the bronchoalveolar lumen and in airway wall tissue, whereas infiltration of lymphocytes or macrophages remained unchanged. The reduction in eosinophil infiltration was accompanied by normalization of AHR and prevention of goblet cell hyperplasia, indicating reduced mucus production. Furthermore, antagonizing CCR-3 prevented airway remodeling as defined by subepithelial fibrosis and increased accumulation of myofibrocytes in the airway wall of chronically challenged mice. These data demonstrate that antagonism of CCR3 reduces eosinophil numbers, which is accompanied by diminution of asthma pathology in a mouse model of established chronic experimental asthma. Therefore, antagonizing CCR-3 represents a new approach toward a promising asthma therapy.
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PMID:Effects of a low-molecular-weight CCR-3 antagonist on chronic experimental asthma. 1691 75

Chemokine CC motif receptor-like 2 (CCRL2) is a heptahelic transmembrane receptor that shows the highest degree of homology with CCR1, an inflammatory chemokine receptor. CCRL2 mRNA was rapidly (30 minutes) and transiently (2-4 hours) regulated during dendritic cell (DC) maturation. Protein expression paralleled RNA regulation. In vivo, CCRL2 was expressed by activated DC and macrophages, but not by eosinophils and T cells. CCRL2(-/-) mice showed normal recruitment of circulating DC into the lung, but a defective trafficking of antigen-loaded lung DC to mediastinal lymph nodes. This defect was associated to a reduction in lymph node cellularity and reduced priming of T helper cell 2 response. CCRL2(-/-) mice were protected in a model of ovalbumin-induced airway inflammation, with reduced leukocyte recruitment in the BAL (eosinophils and mononuclear cells) and reduced production of the T helper cell 2 cytokines, interleukin-4 and -5, and chemokines CCL11 and CCL17. The central role of CCRL2 deficiency in DC was supported by the fact that adoptive transfer of CCRL2(-/-) antigen-loaded DC in wild-type animals recapitulated the phenotype observed in knockout mice. These data show a nonredundant role of CCRL2 in lung DC trafficking and propose a role for this receptor in the control of excessive airway inflammatory responses.
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PMID:Nonredundant role of CCRL2 in lung dendritic cell trafficking. 2060 67