Antiretroviral treatment reverses HIV-induced reduction in the expression of surface antigens on alveolar macrophages in AIDS patients

Abstract

StMMARYMoAbs and itnmunopcroxidasc tiielhods were used to Identify antigen-presenting and phagocytic cells and lo assess expression of HLA-DR molecules on cells obtained by bronehoalveolar iavagc (BAD from 33 AIDS patients and nine normal volunteers. In I7patienls, not receiving antiretroviral Iherapy, lhe expression of HLA-DR tnoleeulcs (MoAb RFDRl) as well as the percentages oi'eells expressing RFDI marker for antigen-presenting cells and RFD7 marker for mature phagocytes were significantly rcdueed. However, in BAL obtained after commencing treatment with zidovudine (AZT)in2l patients or with 2'.3'-dideoxyinosinc(DDI)in five patients, the expression of the tnarkers studied was found to have returned to levels of expression seen in normal lavages. The changes observed were clearly associated with antirelroviral treatment and did tioteorrelale with applications ofother drugs, blood CD4 counts or presence of infectious organisms in BAL fluid. As lhe alterations in the expression of HLA-DR molecules and RFDI marker on macrophages have been shown lo be assoeialed wiih functional capacities of these cells, the reversal of impaired expression ofphenolypic markers on alveolar macrophages in A IDS patients by AZT and DDI signifies an important ability of these drugs to modify immune reactivity and emphasizes the need to monitor such functions in HIV disease. treatment reduces frequency of opportunistic infections [9.10], but il is not known whether antirelroviral treatment can alTeel functional capacities of maerophages. In order to establish lhe effect of such treatment, we studied the expression of cell markers, believed lo be associated wiih function on alveolar macrophages in three groups of HIV-infected patients presenting with pneumonitis; (i) individuals not receivinganliretroviral drugs, and (ii) patients treated with AZT, or (iii) with 2',3'-dideoxyinosine (DDI), Keywords MATERIALS AND METHODS Brtincliotilrciiltir linage and study popidaiionBronchoalveotar lavagc (BAL) of lhe appropriate lobe (as indicated by radiographic abnormality) or of the right middle lobe (in palients wiih normal radiographs or generalized radiographic shadowing) was carried out using a fibreopiie bronchoscopc. A subsegmcntal bronchus was anaesthetized using 2",. lignoeaine and lavaged with 20-ml aliquots of O9'M, saline (buffered to pH 7-4 with NaHCO,) to a loial of 180 ml. The lavage fluid was gently aspirated after each aliquot and collected into a sterile, siliconizcd glass bottle maintained at 4 C. 13

Myeloid Cells in Cancer Progression: Unique Subtypes and Their Roles in Tumor Growth, Vascularity, and Host Immune Suppression

“…Abbreviations: HSCs, Hematopoietic Stem Cells; MPPs, MultiPotential Progenitors; CLPs, Common Lymphoid Progenitors; GMPs, Granulocyte/Macrophage Progenitors; MEPs, Megakaryocyte/Erythroid Progenitors; CMPs, Common Myeloid Progenitors; MDPs, Macrophage and Dendritic-cell Progenitors. See [ 16 , 18 – 25 , 30 , 32 , 37 , 39 , 40 , 44 , 45 , 112 – 120 ] …”

“…Other aspects of the M2 immunosuppressive phenotype may be regulated by NF-kB signaling whereas the proangiogenic properties of the M2 TAMs are regulated by other signals [ 111 ]. Other unique myeloid populations, such as TEMs and MDSCs, are thought to be present in the circulation and get recruited to the tumor site [ 66 , 101 , 112 ]. Many factors, such as VEGF, have been implicated with accumulation of several myeloid subtypes [ 4 , 97 ].…”