Interaction of macrophages with apoptotic cells enhances HIV Type 1 replication through PGE2, PAF, and vitronectin receptor.
Phagocytosis of apoptotic cells by macrophages increases secretion of soluble mediators and generates an antiinflammatory environment. We previously reported that phagocytosis of apoptotic cells by HIV-1-infected macrophages enhances viral replication, with the participation of the cytokine transforming growth factor- beta1 and an integrin receptor. Now, we describe the role of prostaglandin E2 (PGE2), platelet-activating factor (PAF), and the integrin alphaVbeta3 (vitronectin receptor, VnR) in this phenomenon. Exacerbation of HIV-1 growth induced by phagocytosis of apoptotic cells was inhibited when HIV-1-infected macrophages were treated with a cyclooxygenase 2 inhibitor, or with a PAF receptor antagonist (BN 52021) immediately after macrophage interaction with apoptotic cells. Treatment of HIV-1-infected macrophages with BN 52021 decreased viral replication, whereas addition of PGE2 or PAF to these cells enhanced viral replication. Monoclonal antibodies (MAbs) to VnR reduced the macrophage uptake of apoptotic cells, prevented the enhancement of HIV-1 growth upon the engulfment of apoptotic cells, and potently augmented viral replication in HIV-1-infected macrophages in the absence of apoptotic cells. In conclusion, PGE2 and PAF, and ligation of VnR as well, contribute to amplify viral growth in HIV-1-infected macrophages upon uptake of apoptotic cells.
Lima
Rosangela G
RG
Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, BA, Brazil.
Moreira
Letícia
L
Paes-Leme
Joana
J
Barreto-de-Souza
Victor
V
Castro-Faria-Neto
Hugo C
HC
Bozza
Patrícia T
PT
Bou-Habib
Dumith Chequer
DC
D017209:Apoptosis / Q000276:immunology; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology; D046934:Ginkgolides; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007783:Lactones / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology / Q000821:virology; D010587:Phagocytosis / Q000187:drug effects* / Q000502:physiology; D010972:Platelet Activating Factor / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
D016861:Cyclooxygenase Inhibitors; D004224:Diterpenes; D046934:Ginkgolides; D039302:Integrin alphaVbeta3; D007783:Lactones; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011720:Pyrazoles; D043562:Receptors, G-Protein-Coupled; D013449:Sulfonamides; C039351:platelet activating factor receptor; C045856:ginkgolide B; D000068579:Celecoxib; D015232:Dinoprostone