论文部分内容阅读
Acute painful vaso-occlusive crises and recurrent infections are frequent complications of patients with sickle cell disease (SCD).Chronic activation of monocytes producing pro-inflammatory cytokines may play a role in immune dysregulation, increased susceptibility to infection, activation of vascular endothelium, and vaso-occlusion in SCD.The pathophysiology of SCD may be influenced by activated and/or immature monocytes.Our study compared activated monocytes in SCD with normal monocytes in healthy persons, analyzing CD4, CD 14, CD 16, and HLADR antigen expression using flow cytometry as well as morphologic assessment of monocytes with Wright and alphanaphthyl butyrate esterase (ANBE) stains.SCD patients showed absolute monocytosis, in which monocytes displayed marked decreased CD4+, CD4+HLA-DR+ and CD4+CD14+ expression and increased CD 14(dim)+CD 16+ expression.Monocytes in SCD show immature morphology, including a high N/C ratio, indented nuclei, decreased cytoplasmic vacuolation, as well as markedly decreased ANBE activity.These altered properties of monocytes may play a role in the pathophysiology of impaired immune response, recurrent infectious disease, and vaso-occlusive crises in SCD.We also examined the function of antigen-presenting dendritic cells in SCD.Peripheral blood dendritic cells (PBDC) were purified from patients with steady-state SCD and from healthy donors.Monocyte-derived DC (MoDC) from patients and donors were generated in vitro with granulocyte/macrophage colony stimulating factor (GMCSF) and intefleukin-(IL-)-4.Compared to those from healthy donors, PBDC from patients with SCD showed reduced expression of HLA-DR, CD80, CD86, and CD40;reduced stimulatory capacity to mixed lymphocyte reactions (MLR);and reduced production of IL-12 in response to lipopolysaccharide (LPS) and to CD40 ligand.Similar reductions were observed in MoDC derived from patients with SCD.These results also indicate that alterations in dendritic cell function are present in patients with SCD.These alterations in both monocytes and dendritic cells in SCD may contribute to the observed deficiencies in immune response and susceptibility to infection.