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Dysregulation of Vasodilatory Pathways is a Contributory Factor to Acute Chest Syndrome
Author(s) -
Frazier Krystle,
Young Sheila M,
Cook Kayleigh,
Ibe Basil Obijiaku
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1016.12
Subject(s) - medicine , acute chest syndrome , endothelial dysfunction , endothelium , inflammation , immunology , prostacyclin , fibrinolysis , disease , sickle cell anemia
Acute chest syndrome (ACS), the second most common cause of hospitalization for sickle cell disease (SCD) patients and cause for 25% of premature death cases, remains a therapeutic challenge due to the unknown nature of the syndrome's development. SCD patients exhibit a baseline leukocytosis, or pro‐inflammatory state, that increases their risk of developing ACS. Red blood cells (RBC) of SCD patients induce injury to the lung microvasculature resulting in the release of clotting factors and inflammatory mediators. Our hypothesis is that these mediators sustain pulmonary endothelial injury and RBC adhesion to the vessel wall resulting in pulmonary vascular occlusion and ultimately ACS. Objective To investigate a mechanism by which RBCs stimulate production and release of inflammatory cytokines and proteins in SCD. Methods Studies were conducted on human pulmonary microvascular endothelial cells (HPMEC) with and without overlay with RBCs or neutrophils of SCD patients in the steady state. Inflammatory mediators were measured by ELISA or Western blotting. Data were analyzed statistically at p<0.05. Results HPMEC cultured with RBCs from SCD patients released 40% more leukotriene C 4 and 6‐fold more 11β‐PGF 2α and more TxA 2 than controls. Release of prostacyclin by SCD RBC blood was not different from control. Conclusions Sickle cell mutation‐bearing erythrocytes cause release of inflammatory mediators that activate vasoconstrictive pathways in HPMEC and down‐regulate vasodilatory pathways. This condition may eventually overwhelm the ability of the HPMEC to secrete vasodilators. A closer look at the interaction of these mediators and microvascular endothelium may reveal genetic polymorphisms and provide a potential for therapeutic targeting with gene silencing technology. Support or Funding Information AMA Foundation