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MFG-E8 and Acute Lung Injury

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MFG-E8 and Inflammation

Abstract

Although milk fat globule-epidermal growth factor-factor 8 (MFG-E8) was initially identified as a pivotal factor for the clearance of apoptotic cells, subsequent studies revealed its diverse cellular functions which is not only confined to the development of systemic lupus erythematosus (SLE), but also other systemic and localized acute inflammatory diseases. Herein, we have described the promising role of MFG-E8 in terms of attenuating the consequences of acute lung injury (ALI) in several animal models adopted by either direct lipopolysaccharide (LPS) instillation or indirectly via clinically relevant approaches, e.g., sepsis, ischemia-reperfusion, and hemorrhages. Current chapter emphasizes the pathophysiology of ALI and the implications of MFG-E8 mode of actions towards implementing it as a potential therapeutic target to improve disease prognosis in critically ill patients.

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Abbreviations

ALI:

Acute lung injury

ARDS:

Acute respiratory distress syndrome

CLP:

Cecal ligation and puncture

GRK2:

G-protein coupled receptor kinase 2

I/R:

Ischemia/reperfusion

ICAM-1:

Intercellular adhesion molecule-1

IFN-γ:

Interferon-γ

LAD:

Leukocyte adhesion deficiency

MFG-E8:

Milk fat globule-epidermal growth factor-factor 8

MMP:

Matrix metalloproteinases

MPO:

Myeloperoxidase

NF-κB:

Neuclear factor-κB

NOS:

Nitric oxide synthase

PS:

Phosphatidylserine

RGD:

Arginine-glycine-aspartate

ROS:

Reactive oxygen species

TLR:

Toll like receptor

TUNEL:

Terminal deoxynucleotidyl transferase dUTP nick end labeling

VCAM-1:

Vascular cell adhesion molecule-1

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Acknowledgements

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

Conflict of Interest 

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. M. Aziz reports no financial conflicts of interest.

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Authors and Affiliations

  1. Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA

    Monowar Aziz PhD & Ping Wang MD

  2. Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, NY, 11030, USA

    Monowar Aziz PhD & Ping Wang MD

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  1. Monowar Aziz PhD
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Correspondence to Ping Wang MD .

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  1. Center for Translational Research, The Feinstein Inst. for Medical Research, Manhasset, New York, USA

    Ping Wang

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© 2014 Springer Science+Business Media Dordrecht

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Aziz, M., Wang, P. (2014). MFG-E8 and Acute Lung Injury. In: Wang, P. (eds) MFG-E8 and Inflammation. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8765-9_9

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