Temporal production of CCL28 corresponds to eosinophil accumulation and airway hyperreactivity in allergic airway inflammation.
CCL28 is a recently identified chemokine ligand for CCR10 and CCR3 that has been identified in mucosal epithelial surfaces in diverse tissues. CCL28-mediated eosinophil chemotaxis and peroxidase release were inhibited by preincubation of cells with anti-CCR3. CCL28 was constitutively expressed in lung tissue collected from nonsensitized control mice but increased levels were found in mice sensitized and rechallenged with cockroach antigen (CRA). CCL28 levels peaked in the lungs 24 hours after intratracheal challenge with CRA, whereas eotaxin expression peaked at 8 hours. Increased expression of CCR3 but not CCR10 could be detected during the induction of the CRA-induced pulmonary inflammation. To investigate the role of CCL28 in allergic airway responses, mice were treated with CCL28 antiserum 1 hour before receiving the final CRA challenge. The level of airway hyperresponsiveness in mice treated with anti-CCL28 was significantly reduced at 24 hours, but not 8 hours, compared to mice receiving control serum. This reduction was not related to decreased Th2 cytokine, chemokine, or leukotriene levels at 24 hours although peribronchial eosinophilia was significantly reduced. Thus, CCL28 appears to play a role in regulating eosinophil recruitment to peribronchial regions of the lung possibly by coordinated temporal production with eotaxin.
John
Alison E
AE
Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor MI 48109-0602, USA.
Thomas
Molly S
MS
Berlin
Aaron A
AA
Lukacs
Nicholas W
NW
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000378:metabolism* / Q000473:pathology; D054413:Chemokine CCL11; D018925:Chemokines / Q000096:biosynthesis* / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D002633:Chemotaxis; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000378:metabolism*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007249:Inflammation; D017997:Leukotriene C4 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008024:Ligands; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D010544:Peroxidases / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D054447:Receptors, CCR10; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D013997:Time Factors
C515456:CCL11 protein, human; C414047:CCL28 protein, human; C515706:CCR10 protein, human; C515350:CCR3 protein, human; C515457:Ccl11 protein, mouse; C515707:Ccr10 protein, mouse; C515351:Ccr3 protein, mouse; D054413:Chemokine CCL11; D018925:Chemokines; D019742:Chemokines, CC; D015289:Leukotrienes; D008024:Ligands; D054447:Receptors, CCR10; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D017997:Leukotriene C4; D012313:RNA; D010544:Peroxidases