Differential Roles of Macrophages in Diverse Phases of Skin Repair

Lucas, Tina; Waisman, Ari; Ranjan, Rajeev; Roes, Jürgen; Krieg, Thomas; Müller, Werner; Roers, Axel; Eming, Sabine A.

doi:10.4049/jimmunol.0903356

Cited by 1,007 publications

(969 citation statements)

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“…4,5 Briefly, mice were treated with thioglycolate for 3 days. Macrophages were obtained by peritoneal lavage and were cultured in RPMI 1640 medium (Invitrogen, Carlsbad, CA) containing glucose at different concentrations; nonadherent cells were deleted by changing the culture medium.…”

Section: Cell Culturesmentioning

confidence: 99%

“…Under the same conditions, 14R,21R-diHDHA and 14R,21S-diHDHA were generated from 14R-HDHA by h-P450. 8 14S-HDHA or 14S-HDHA-d 5 were prepared by incubating DHA or DHA-d 5 (50 g each), respectively, with porcine L-12-LOX (1000 U) in buffer containing 0.1 mol/L Tris at pH 7.4 for 20 minutes at 37°C. At the end of the incubation, 3 mg of NaBH 4 was added.…”

Section: Cell Culturesmentioning

confidence: 99%

“…The biosynthesis of 14S,21R-diHDHA and intermediates was assayed by incubating (20 minutes) purified macrophages, PMNs, lymphocytes (T cells/B cells 1:1), fibroblast cells, or DMVECs (1 ϫ 10 7 cells/each type), as well as platelets (1 ϫ 10 8 cells), in PBS containing DHA (3 mol/L) or 14S-HDHA-d 5 (1 mol/L); this was followed by stimulating the cells (37°C, 1 hour) with TNF␣ (10 ng/mL), IL-1␤ (10 ng/mL), and lipopolysaccharide (100 ng/mL). LC-MS/MS analysis indicated that DHA (free acid) in fullthickness murine skin wounds can reach levels as high as 1 to 9 mol/kg.…”

Section: Cell Culturesmentioning

confidence: 99%

“…2 Macrophage prohealing functions have been confirmed: macrophage transplantation into wounds promotes healing, 3,4 and macrophage depletion results in delayed wound healing. 5,6 The presence of diabetes, however, compromises macrophage functions and so contributes to disrupted wound healing. 1,4,7 In addition to amino acid-based cytokines and growth factors, which are known to mediate wound healing and associated angiogenesis, lipid-derived molecules also may be important mediators.…”

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confidence: 99%

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Autacoid 14S,21R-Dihydroxy-Docosahexaenoic Acid Counteracts Diabetic Impairment of Macrophage Prohealing Functions

Tian

Lü

Shah

et al. 2011

The American Journal of Pathology

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Impaired macrophage functions imposed by diabetic complications and the suppressed formation of 14S, 2 1 R -d i h y d r o x y d o c o s a -4 Z , 7Z , 1 0 Z , 1 2 E , 1 6 Z , 19Z-hexaenoic acid (14S,21R-diHDHA) in wounds contribute significantly to deficient wound healing in diabetics, but how are macrophage functions and 14S,21R-diHDHA formation associated? We studied 14S,21R-diHDHA generation from macrophages using liquid chromatography/mass spectrometry. The role in macrophage-mediated wound healing functions was determined using a murine splinted excisional wound healing model and in vitro assays. 14S,21R-diHDHA acts as a macrophage-generated autacoid, and its attenuated formation in macrophages of diabetic db/db mice was accompanied by impairment of macrophage prohealing functions. 14S,21R-diHDHA restored db/db macrophage-impaired prohealing functions by promoting wound re-epithelialization, formulation of granulation tissue, and vascularization. Additionally, 12/15-lipoxygenase-deficient macrophages, which are unable to produce 14S,21R-diHDHA, exhibited impaired prohealing functions, which also were restored by 14S,21R-diHDHA treatment. The molecular mechanism for 14S,21R-diHDHA-induced recovery of impaired prohealing functions of db/db macrophages involves enhancing their secretion of vascular endothelial growth factor and platelet-derived growth factor BB, decreasing hyperglycemia-induced generation of reactive oxygen species, and increasing IL-10 expression under inflammatory stimulation. Taken together, these results indicate that deficiency of 14S,21R-diHDHA formation by diabetic macrophages contributes to their impaired prohealing functions. Our findings provide mechanistic insights into wound healing in diabetics and suggest the possibility of using autologous macrophages/monocytes, treated with 14S,21R-diHDHA, or related compounds, to promote diabetes-impaired wound healing. (Am J Pathol

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Section: Cell Culturesmentioning

confidence: 99%

Section: Cell Culturesmentioning

confidence: 99%

Section: Cell Culturesmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Autacoid 14S,21R-Dihydroxy-Docosahexaenoic Acid Counteracts Diabetic Impairment of Macrophage Prohealing Functions

Tian

Lü

Shah

et al. 2011

The American Journal of Pathology

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“…Adult mouse [16] Macrophages play critical roles in skeletal muscle regeneration Adult mouse [50,58] Macrophages exert specific roles at diverse stages of repair and orchestrate the natural sequence of repair phases in skin Adult mouse [4,[17][18][19] Gr-1 + CD11b + cells contribute to injury-induced neo-vascularization Adult mouse [42] Non-inflammatory Ly6C low MHCII high wound macrophages promote wound healing Adult mouse [43] Persisting pro-inflammatory macrophages impair wound healing in venous Ulcers Human [40] classical/alternative macrophage activation is operative at the cutaneous wound site and which of the micro-environmental cues may direct macrophage activation. Furthermore, the functional relation between the recruitment of diverse blood monocyte subtypes into damaged tissue and their potential activation to the alternative or classical macrophage phenotype was unclear.…”

Section: Macrophage Plasticity and Polarizationmentioning

confidence: 99%

Macrophages – sensors and effectors coordinating skin damage and repair

Willenborg

Eming

2014

J Deutsche Derma Gesell

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SummaryRestoration of skin integrity and homeostasis following injury is a vital process. Wound healing disorders, including chronic skin ulcers and pathological scarring, are of major clinical impact. The current therapeutic approaches are often not sufficient. The development of novel efficient therapies requires a thorough understanding of the underlying molecular mechanisms. A cardinal feature of non-healing skin ulcers and excessive scarring is a prolonged inflammatory response at the wound site, which aborts the healing response. Modulation of the local immune response may be an effective therapeutic strategy to correct impaired healing conditions. Yet, the specific mechanisms of inflammation, particularly the role of the diverse leukocyte lineages attracted to the site of tissue damage, have not been resolved. Recent findings in diverse experimental model systems and clinical studies have refined the understanding of monocyte/macrophage biology and the role of cells of the monocytic lineage in tissue regeneration. Thus, monocytes/macrophages are emerging as novel and interesting therapeutic targets to interfere in wound healing pathologies. In this article we will review the role of monocytes/macrophages in skin repair in the light of the recent literature and findings from our own group. This article will provide a rationale for monocyte/macrophage-based therapies to facilitate the healing response.

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