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Review: milk fat globule-EGF factor 8 expression, function and plausible signal transduction in resolving inflammation

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Abstract

Although the cloning and molecular characterization of MFG-E8 was first reported in the early 90s, breakthrough on MFG-E8 research came into light when it was explored as an outstanding factor for phagocytosis of apoptotic cells by professional macrophages in 2002. Since then numerous studies have been performed on MFG-E8 not only to demonstrate the role of phagocytic clearance of apoptotic cells, but also to focus on a wide range of aspects, even emphasizing on a direct link to innate-immune systems. In terms of its role as therapeutic potentials, our group, as well as others, has shown MFG-E8 to be an essential factor in attenuating inflammation and improving prognosis in several animal models of life threatening diseases. Considering these versatile functions of MFG-E8, several in vitro and in vivo studies were embarked on to explore the mechanistic pathways exerted by MFG-E8 during inflammation. With the relevant cumulative findings, herein we reviewed the potential roles of MFG-E8 in pathophysiological conditions by highlighting its plausible signal-transduction mechanisms.

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Abbreviations

MFG-E8:

Milk fat globule-epidermal growth factor-factor 8

RGD:

Arginine–glycine–aspartate

CLP:

Cecal ligation and puncture

SLE:

Systemic lupus erythematosus

PPAR:

Peroxisome proliferator-activated receptor

HMGB1:

High-mobility group protein B1

AD:

Alzheimer’s disease

ABP:

Amyloid β peptide

VEGF:

Vascular endothelial growth factor

Jak/STAT:

Janus kinase/signal transducer and activator of transcription

SOCS3:

Suppressor of cytokine signaling 3

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Acknowledgments

This study was supported by the National Institutes of Health (NIH) grants, R01 GM 057468 and R33 AI 080536 (P.W.).

Conflict of interest

One of the authors (P Wang) is an inventor of the pending PCT application #WO/2006/122327: “Milk fat globule epidermal growth factor–factor VIII and sepsis” and PCT application #WO/2009/064448: “Prevention and treatment of inflammation and organ injury after ischemia/reperfusion using MFG-E8”. These patent applications cover the fundamental concept of using MFG-E8 for the treatment of sepsis and ischemia/reperfusion injury. Other authors report no financial conflicts of interest.

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Authors and Affiliations

  1. Department of Surgery, North Shore University Hospital and Long Island Jewish Medical Center, 350 Community Dr, Manhasset, NY, 11030, USA

    Monowar Aziz, Asha Jacob, Akihisa Matsuda & Ping Wang

  2. Center for Immunology and Inflammation, The Feinstein Institute for Medical Research, 350 Community Dr, Manhasset, NY, 11030, USA

    Asha Jacob & Ping Wang

  3. Albert Einstein College of Medicine, Department of Surgery, North Shore University Hospital and Long Island Jewish Medical Center, 350 Community Dr, Manhasset, NY, 11030, USA

    Ping Wang

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  1. Monowar Aziz
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  4. Ping Wang
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Correspondence to Ping Wang.

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Aziz, M., Jacob, A., Matsuda, A. et al. Review: milk fat globule-EGF factor 8 expression, function and plausible signal transduction in resolving inflammation. Apoptosis 16, 1077–1086 (2011). https://doi.org/10.1007/s10495-011-0630-0

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