Altered Adhesion Molecule Expression of Leukocytes of SCD Patients in Crisis and Steady State Nagina Parmar 1 , Jamie Hutchison 2 , Gemma Vomiero 3 , Ashok Kumar 6 , Mohamed Abdelhaleem 4 , Isabelle Gaboury 5 , Melanie Kirby-Allen 7 and Robert J. Klaassen 5* 1 Department of Blood Transfusion Medicine, Toronto General Hospital, Toronto, ON, Canada 2 Department of Critical Care, Hospital for Sick Children, Toronto, ON, Canada 3 University of Calgary, Alberta, AB, Canada 4 Division of Haematopathology, Department of Pathology, Hospital for Sick Children, Toronto, ON, Canada 5 Division of Haematology, Department of Paediatrics, Children’s Hospital for Eastern Ontario, Ottawa, ON, Canada 6 Department of Pathology, CHEO Research Institute, Ottawa, ON, Canada 7 Division of Haematology, Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada * Corresponding author: Robert Klaassen, Department of Pediatrics, Division of Hematology/Oncology, Children’s Hospital for Eastern Ontario (CHEO), Rm 5109, 401 Smyth Rd, Ottawa, ON. K1H 8L, Canada, Tel: (613)737-7600 Extn. 2210; Fax: (613)738-4828; E-mail: rklaassen@cheo.on.ca Received date: Feb 17, 2015, Accepted date: Mar 26, 2015, Publication date: Mar 30, 2015 Copyright: © 2015 Parmar N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Background: Sickle cell disease (SCD) patients experience ischemic events resulting from vaso-occlusion of both macro-and microcirculation. A risk factor associated with increased morbidity and mortality is leukocytosis in the absence of infection. This study investigated the role of leukocytes in the pathogenesis of acute sickle cell crisis. Procedure: Children were enrolled at two tertiary care centers in three groups: hemoglobin SS (Hb SS) patients admitted to hospital with an acute crisis, non-crisis or steady state SS patients, and sickle cell screen negative, race- matched controls. Flow cytometry measured cell surface expression of adhesion molecules. Results: 28 Hb SS and 10 control patients were enrolled. Elevated white blood and platelet counts were observed for the crisis children (P<0.01) compared to healthy control children. There was a significant increase in the expression of adhesion molecules on neutrophils and monocytes (CD11, CD 18 and CD-62L) in children in steady state (P<0.05) compared to crisis, and healthy children. 71% of crisis children were receiving non-steroidal anti-inflammatory drugs (NSAIDs) or hydroxycarbamide, whereas none of the patients in steady state were receiving these drugs. Conclusion: Further investigation is needed to explain these findings, but is likely due to the use of NSAIDs and hydroxycarbamide in our crisis patients. Keywords: Leucocytes; Sickle cell disease; Selectin; Integrin Introduction Sickle Cell Disease (SCD) is characterized by the sickling of red blood cells and hemolysis; however inflammatory mechanisms and other types of cells such as leukocytes appear to participate in the vaso- occlusive process. Chronically, patients can develop dysfunction because of recurrent episodes of ischemia, as well as cardiomegaly and hepatic dysfunction secondary to ongoing hemolytic anemia. One of the more frequently observed manifestations of SCD is a repeated episode of pain crisis, which remains one of the most common reasons for hospital admission. Endothelial cell in comparison to many other cell types, were thought to be less active, less complex, and less interesting. Research in this area has expanded dramatically since then, revealing the endothelial lining as an active participant in a wide variety of pathophysiological processes, including inflammation and immunity [1]. Much of this research has been directed towards molecular mechanisms of leukocyte adhesion to the endothelium, and has resulted in the identification, characterization, and cloning of multiple endothelial-surface glycoprotein that support adhesion through an interaction with specific ligands on leukocytes. There are three main molecule-types that play a role in this interaction, namely, (i) the selectins, (ii) the immunoglobulin superfamily molecules, and (iii) the integrins. The expression of these various molecules may be modulated and unregulated by the vascular environment, primarily by toxins and cytokines [2,3]. Recently, investigators have observed interactions between sickle reticulocytes, leucocytes, and endothelial cells via these adhesion molecules in patients with SCD, and hypothesized that these mechanisms may contribute to the pathophysiology of the disease [4-6] Monocytes from patients with SCD have increased expression of IL-1 β, and TNF-α two cytokines that are known to increase the expression of endothelial cell surface receptors [7]. In vivo data has also been generated in sickle cell mice models indicating that leukocytes that are adherent to the vessel wall can directly contribute to vascular occlusion by means of their interactions with sickle Parmar et al., J Blood Disorders Transf 2015, 6:2 DOI: 10.4172/2155-9864.1000262 Research Article Open Access J Blood Disorders Transf ISSN:2155-9864 JBDT, an open access journal Volume 6 • Issue 2 • 1000262 Journal of Blood Disorders & Transfusion J o u r n a l o f B l o o d D i s o r d e r s & T r a n s f u s i o n ISSN: 2155-9864