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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