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Thursday, December 5, 2013

See See How CCL19 Effects Eosinophilic Pneumonia


  
Eosinophils are granulocytes that contain basic granules (i.e. secretory vesicles) that kill large parasites and are linked to various forms of allergies.  Eosinophilic pneumonia (EP) is a broadly defined disease that is characterized by an infiltration of eosinophils in lung alveolar tissue.  EP includes Churg-Strauss Syndrome (a rare autoimmune disease), chronic EP and acute EP (the difference between the two is the presence of eosinophils in the blood/tissues and only the tissue, respectfully).  Individuals with EP are often found to have an increased concentration of macrophages and dendritic cells, important innate immune response mediators.  Symptoms include shortness of breath, weight loss, fever, and even respiratory failure, while causes range from parasitic infection, immune system dysfunction, medication, and environmental stimuli like tobacco smoke and dust.  Although symptoms can be serious, few is known about the cellular mechanisms behind EP, specifically macrophage and DC recruitment into the lungs.  Therefore in response, Nureki et al. investigated EP further by seeing if either, both, or neither CCL19 and CCL21 (molecules that attract motile cells with a specific receptor to a specific location) bound to CCR7 expressed on DCs and macrophages, homing them into the lungs.
In order to extract cells present in alveoli of patients with EP and control individuals as noninvasively as possible, the researchers performed Bronchoalveolar lavage (BAL).  BAL is a procedure in which fluid (BALF) in released into the lungs and recollected (via bronchoscope.  Once BALF was collected, cytokines/chemokines were measured by enzyme-linked immunosorbent assay (ELISA), which is used to measure the concentration of antigens via antibody (complementary binding molecules) detection.  Finally, levels of proteins on cell surfaces were detected by immunocytochemistry, a technique that uses antibody binding and further bound-antibody detection.
Based on ELISA results, both concentrations of CCL19 and CCL21 increased in BALF patients with EP.  Also, levels of CCL19, but not CCL21, were significantly higher in current smokers as compared to nonsmokers and ex-smokers.  Furthermore EP patients who went into remissions had a decrease in BALF CCL19 levels, but not CCL21.  BALF CCL16, CCL17, and CCL22 levels were all significantly higher in EP patients.  Nureki et al. then compared chemokine levels and found that CCL19 levels were positively correlated to levels of CCL16, CCL17, and CCL22 in the BALF of EP patients, while C22 had no significant correlation to CCL16, CCL17, and CCL22.  Finally, Nureki et al. used immunocytochemistry to show that there were no CCL21-positive BALF cells, only CCL19-positive cells.   The large CCL19-positive cells were macrophages while the small CCL19-positive cells were mainly T cells and some immature dendritic cells. 
Although there is a lot of information above, it comes down to the fact that CCL19 contributes to macrophage and DC accumulation and resulting inflammation in EP.  An overview of proposed immune pathway is below.

Clinically these results are important because it identifies CCL19 as a potential target for downregulation/upregulation (it is still unknown if CCL-19 contributes to or alleviate inflammation, but Nureki et al. hypothesizes it worsens EP) in the treatment of EP and other pulmonary inflammatory diseases.  Also, because there was a positive association between CCL19 and CC17 (a Th-2 specific chemokines) there is a possibility it linked to Th-2 accumulation as well. 


REFERENCES:

Main Article:

Nureki S, Miyazaki E, Ishi T, Ito T, Takenaka R, Ando M, Kumamoto T. Elevated concentrations of CCR7 ligands in patients with eosinophilic pneumonia. Allergy 2013; 68: 1387–1395.          


Other References:

Carrington CB, Addington WW, Goff AM, Madoff IM, Marks A, Schwaber JR et al. Chronic eosinophilic pneumonia. N Engl J Med 1969; 280:787-798.

Mak TW, Saunders ME (2011). Primer to the Immune Response. New York, NY: AP Cell

Nureki S, Miyazaki E, Ando M, Kumamoto T, Tsuda T. CC chemokine receptor 4 ligand production by bronchoalveolar lavage fluid cells in cigarette-smoke-associated acute eosinophilic pneumonia. Clin Immunol 2005; 116: 83–93.           

Wechsler, M. (2011, April 18). Eosinophilic Pneumonia. APFED. Retrieved December 3, 2013, from http://apfed.org/drupal/drupal/.


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