Advanced age impairs macrophage polarization. Journal Article


Authors: Mahbub, S.; Deburghgraeve, C. R.; Kovacs, E. J.
Article Title: Advanced age impairs macrophage polarization.
Abstract: Aging affects many aspects of the cellular function of macrophages. Macrophages play a critical role in innate immunity, acting as sentinels to fight pathogens, promoting wound healing, and orchestrating the development of the specific acquired immune response. However, little is known about how age influences the ability of macrophage to change phenotypes in response to environmental factors. This study examined the age-associated defects on macrophage polarization toward a pro-inflammatory (M1) or an anti-inflammatory (M2) phenotype. Adherent splenocytes enriched for macrophages were cultured with or without lipopolysaccharide (LPS), a combination of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha or interleukin (IL)-4. A panel of M1 markers, inducible nitric oxide synthase (iNOS), IL-6, IL-1beta, and TNF-alpha, and M2 markers, including arginase-1 (Arg1), Ym1, and Found In Inflammatory Zone 1 (FIZZ1), were analyzed. IL-6 mRNA in cells from aged mice was decreased by 78% and 58% compared with young after stimulation with LPS or IFN-gamma and TNF-alpha (P0.05), respectively. Also, there was a marked reduction in the induced levels of iNOS, IL-1beta, and TNF-alpha in cells from aged mice relative to young controls. Similarly, IL-4 exposure resulted in a reduction of M2 markers in adherent splenocytes from aged mice compared with younger animals. This was consistent with a 28% decrease in splenic F4/80(+)IL-4R(+) cells in aged mice relative to controls, although IL-4R expression on these cells did not vary between age groups. In contrast, levels of M1 and most M2 markers, save for FIZZ1, in bone marrow-derived macrophages were similar between the age groups, irrespective of stimuli. These data imply that impaired macrophage polarization in the elderly may dysregulate the development of the host response, making them more susceptible to infectious diseases and that the aging microenvironment may be a key modulator of these macrophage-elicited responses.
Keywords: Female; Surgery; Cytokines; Animals; Mice; Age Factors; Aging; Macrophages; Bone Marrow Cells; Macrophage Activation; Mice, Inbred BALB C; Nitric Oxide Synthase Type II; Receptors, Interleukin-4; Spleen
Journal Title: Journal of Interferon Cytokine Research
Volume: 32
Issue: 1
ISSN: 1557-7465
Publisher: Unknown  
Journal Place: United States
Date Published: 2012
Start Page: 18
End Page: 26
Language: English
DOI/URL:
Notes: ID: 12321; Record Owner: From MEDLINE, a database of the U.S. National Library of Medicine.; Status: MEDLINE; Publishing Model: Journal available in: Print-Electronic Citation processed from: Internet; NLM Journal Code: cd4, 9507088; Other ID: Source: NLM. PMC3255514 [Available on 01/01/13]; CAS Registry/EC Number/Name of Substance: 0 (Cytokines). 0 (Receptors, Interleukin-4). EC 1-14-13-39 (Nitric Oxide Synthase Type II).; Grant Number: AG018859 (United States NIA NIH HHS); Electronic Date of Publication: 20111216; Entry Date: 20120507