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Two-photon Intravital Imaging of Leukocytes During the Immune Response in Lipopolysaccharide-treated Mouse Liver

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Imaging Lymphoid Cell Death In Vivo During Polymicrobial Sepsis.

Lin Zou¹, Howard H Chen, Dan Li

¹1Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 2Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 3Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA.

Critical Care Medicine

|September 4, 2015

Summary

This summary is machine-generated.

Near-infrared annexin V (AV-750) imaging noninvasively detects lymphoid cell death in sepsis. This method correlates with sepsis severity and organ-specific apoptosis, offering clinical potential for early detection.

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Area of Science:

Immunology
Cell Biology
Medical Imaging

Background:

Lymphoid organ cell death contributes to immunosuppression and mortality in sepsis.
Early, noninvasive detection of lymphoid cell death is clinically significant.

Purpose of the Study:

To evaluate in vivo imaging of lymphoid cell death using near-infrared annexin V (AV-750) during polymicrobial sepsis.

Main Methods:

Polymicrobial sepsis was induced in C57BL/6J wild-type and toll-like receptor 3 knockout mice.
In vivo, ex vivo, and flow cytometry imaging of fluorescent AV-750 accumulation was used to detect lymphoid cell death.
Apoptosis was assessed via caspase-3 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining.

Main Results:

Severe sepsis induced significant apoptosis in the thymus, spleen, and liver.
Increased AV-750 fluorescent signal in vivo correlated with sepsis severity and organ-specific cell death.
Toll-like receptor 3 knockout mice showed reduced AV-750 signal and splenocyte death compared to wild-type mice.

Conclusions:

In vivo AV-750 imaging offers spatially resolved, organ-specific detection of lymphoid cell death in sepsis.
AV-750 fluorescent intensity correlates with sepsis severity and lymphoid cell death in the thymus and spleen.