Role of Ferroportin in Macrophage-Mediated Immunity
Year: 2010
Type: article
Abstract: Perturbations in iron metabolism have been shown to dramatically impact host response to infection. The most common inherited iron overload disorder results from defects in the HFE gene product, a major histocompatibility complex class I-like protein that interacts with transferrin receptors. HFE-associated hemochromatosis is characterized by abnormally high levels of the iron efflux protein ferroportin. In this study, J774 murine macrophages overexpressing ferroportin were used to investigate the influence of iron metabolism on the release of nitric oxide (NO) in response to infection. Overexpression of ferroportin significantly impaired intracellular Mycobacterium tuberculosis growth during early stages of infection. When challenged with lipopolysaccharide (LPS) or M. tuberculosis infection, control macrophages increased NO synthesis, but macrophages overexpressing ferroportin had significantly impaired NO production in response to LPS or M. tuberculosis. Increased NO synthesis in control cells was accompanied by increased iNOS mRNA and protein, while upregulation of iNOS protein was markedly reduced when J744 cells overexpressing ferroportin were challenged with LPS or M. tuberculosis, thus limiting the bactericidal activity of these macrophages. The proinflammatory cytokine gamma interferon reversed the inhibitory effect of ferroportin overexpression on NO production. These results suggest a novel role for ferroportin in attenuating macrophage-mediated immune responses.
Source: Infection and Immunity
DOI: 10.1128/iai.00498-10
Institutions: Harvard University, Massachusetts General Hospital
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1199664532, Training Program in Environmental Health Sciences, MACROPHAGE IRON METABOLISM AND TUBERCULOSIS INFECTION, Microgial Iron Metabolism and Its Regulation by Cannabinoids, Manganese Transport and Toxicity, Interdisciplinary Training in Genetics and Complex Disease(RMI), G8755088168, G9000317563, Center for the Study of Inflammatory Bowel Disease at Massachusetts General Hospital, Boston Area Nutrition Obesity Research Center (NORC)
OpenAlex ID: W2118427665