Papel do HEME (Ferro protoporfirina IX) na Resposta Inflamatória: mecanismos moleculares envolvidos no recrutamento de neutrófilos

• Ano de defesa: 2005
• Autor(a) principal: Porto, Bárbara Nery
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal Fluminense; Programa de Pós-graduação em Patologia; Patologia; BR; UFF
• Palavras-chave em Português: Medicina; Patologia experimental; Síndrome séptica; Heme; Neutrófilos; Medicina experimental; Inflamação; Receptor quimiotático; CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA::IMUNOLOGIA CELULAR
• Link de acesso: https://app.uff.br/riuff/handle/1/17571

Heme (Iron Protoporphyrin IX), a ubiquitous molecule present in organisms of all kingdoms, is composed of an atom of iron linked to the four ligand groups of porphyrin. As a prosthetic moiety on inactive apo-heme proteins, heme provides a wide range of biological functions determined in part by the polypeptide associated to it. Diseases of increased hemolysis or extensive cell damage can lead to high levels of free heme, as sickle cell anemia, malaria, hemorrhagic fevers, and sepsis. Heme induces oxidative stress and has several proinflammatory activities. A hallmark of the inflammatory response is the recruitment of leukocytes out of the vasculature to tissues. Heme seems to affect this process in several ways: a) inducing cell adhesion molecule expression on endothelial cells in vitro or in vivo; b) increasing vascular permeability; c) enhancing chemokine expression and secretion; d) inducing migration of leukocytes in vivo and in vitro. The mechanism by which heme activates cells of the innate immune system causing inflammation is not fully characterized. We have recently observed that heme activates macrophages through TLR-4. Considering that heme induces neutrophil migration in vitro, we hypothesize that heme has a direct chemotactic effect on this leukocyte through activation of a G protein coupled receptor. In the present work we show that heme induces neutrophil migration in vivo and in vitro and stimulates the secretion of the inflammatory cytokines, IL-6 and TNF-a, in a dose-dependent fashion. Blood, hemoglobin and diverse heme analogs are also able to induce neutrophil recruitment. In contrast, biliverdin and mesoporphyrins are not efficient to recruit neutrophil and mesoporphyrin treatment in vivo inhibits the heme-induced neutrophil migration. Finally, the chemotactic effect of heme was abolished by pertussis toxin treatment in vitro . Taken together, these results suggest that heme induces neutrophil chemotaxis by activation of a G protein coupled receptor.