Abstract

Vascular occlusions (VOC) underlie most of the acute and chronic sickle cell anemia (SCA) clinical complications and have been correlated to soluble adhesion molecules up regulation and leukocyte activation. A sequential process involving adhesion through selectins and integrins governs leukocyte recruitment to activated endothelium and to sickle red blood cells (RBC), resulting in heterotypic aggregation and VOC. The chronic hemolysis is the major cause of oxidative stress and it can induce transcriptions factors involved in the recruitment of adherent leukocytes in venules. In this work, we assessed the inflammatory potential of leukocytes in venous blood samples by examining cell surface antigens expression by flow cytometry, activation state and its association with hemolytic state in SCA patients group. The study was approved by the FIOCRUZ ethical committee and informed consents were signed by patients or official responsible. Leukocytes were obtained from 22 SCA patients and 22 healthy controls after RBC lyses and labeled with monoclonal anti-CD11b, anti-CD18, anti-CD32, anti-CD62L (L-Selectin) and anti-CD62P (P-Selectin). Leukocyte activation was stimulated by LPS. Statistical analyses were performed using SPSS version 9.0. The basal expression levels on leukocytes cell surface antigens from patients were not different from the control group. However, the CD62L expression levels were associated to C-reactive protein (CRP) higher levels and decrease of fetal hemoglobin in SCA patients (p=0.012). The SCA patients had higher CRP levels when compared to reference levels. Moreover, the data showed a co-expression of CD11b with CD18 (p<0.0001) and CD62P (p=0.011).The platelet count was positively correlated to CD11b expression (p=0.016) and the alanine transaminase high levels with the CD62P expression (p=0.012). Our results demonstrate a leukocyte chronic activation state by expression of CD62L related to CRP higher levels. Interestingly, the platelets could be activated by the indirect activation of CD62P by CD11b, participating of the inflammation state presents at vaso-occlusive events. It seems that the stress oxidative generated by the hemolytic state can contribute to endothelial dysfunction and vaso-occlusive events by CD62L activation in SCA. Fetal hemoglobin is a prognostic factor for several sickle cell complications and we showed that it can ameliorate the CD62L expression on leukocytes, decreasing the chronic inflammatory state of this disease. CD62L serves to as a homing receptor for naïve T lymphocytes and dendritic cells to lymph nodes, mediating the biding of T cells to high endothelial venules, in this view, this can be important marker to inflammatory state and vascular complications in SCA.

Disclosures: No relevant conflicts of interest to declare.

Author notes

Corresponding author