Neutrophil heterocellular aggregates in sickle cell disease: a possible target for cGMP-AMPLIFYING agents?

• Grant number: 12/21702-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: March 01, 2013
• End date: August 31, 2013
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Nicola Amanda Conran Zorzetto
• Grantee: Venina Marcela Dominical
• Supervisor: Gregory J. Kato
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: National Institutes of Health, Bethesda (NIH), United States
• Associated to the scholarship: 10/18386-4 - Heterotypic interactions of neutrophils under inflammatory conditions, BP.DR

Abstract

Sickle cell anemia (SCD) is an inherited hemoglobinopathy that affects millions of people around the world; vaso-occlusive crises are the leading cause of morbidity of this disease. In the scenario of SCD inflammation, neutrophils are activated and have the ability to interact with other blood cells, exerting pathophysiological events within the vascular lumen and may initiate the SCD vaso-occlusive process. The formation of neutrophil-platelet aggregates is well known in vascular diseases and these aggregates may contribute to the vascular inflammation and tissue injury that occurs in SCD. However, there are no studies evaluating the nature and formation of neutrophil-RBCs aggregates in peripheral blood in this pathology. Recently, nitric oxide (NO)-dependent signaling has raised considerable interest as a new strategy for the SCD treatment.Thus, the aim of this placement is to verify, using multispectral imaging flow cytometry (ImageStream flow cytometer; Amnis Corp. Seattle, WA, USA), the presence of erythrocyte-neutrophil and platelet-neutrophil aggregates in peripheral blood obtained from SCD patients and compare with those of healthy individuals. We also wish to observe the adhesion molecules involved in these interactions by fluorescent labeling and inhibition of certain integrins (VLA-4 or Lu/BCAM on RBCs and LFA-1 or Mac-1 on neutrophils) and evaluate the influence of agents that increase the levels of nitric oxide (NO) and the NO second messenger, cGMP. (AU)