Polymicrobial sepsis disrupts normal neutrophil extracellular matrix protein interactions

Area of Science:

• Immunology
• Sepsis Pathophysiology
• Cellular Biology

Background:

• Polymorphonuclear leukocytes (PMNs) are critical immune cells involved in combating infections.
• Extracellular matrix (ECM) proteins, such as fibronectin and laminin, can influence PMN function.
• Intra-abdominal sepsis is a severe condition that can compromise immune responses.

Purpose of the Study:

• To investigate the impact of intra-abdominal sepsis on the function of PMNs adhering to ECM proteins.
• To determine how fibronectin and laminin affect PMN candidacidal activity and activation in the context of sepsis.

Main Methods:

• Two groups of swine were studied: a control group (sham laparotomy) and a sepsis group (cecal ligation and incision).
• PMN candidacidal activity was assessed using 51Cr release assay.
• PMN priming and activation were evaluated by measuring adherence to ECM proteins, CR1/CR3 expression, and production of myeloperoxidase and hypochlorous acid.

Main Results:

• In control animals, fibronectin and laminin significantly enhanced PMN candidacidal activity and activation.
• In septic animals (post-operative day 8), the enhancing effects of fibronectin and laminin on PMN candidacidal activity were abolished.
• While sepsis did not affect PMN adherence or CR1/CR3 expression in response to ECM proteins, it significantly reduced PMN activation (MTT-Formazan, myeloperoxidase, HOCl production).

Conclusions:

• Untreated intra-abdominal sepsis partially abrogates the beneficial effects of ECM proteins on PMN function.
• Specifically, sepsis reduces the activation of PMNs by fibronectin and laminin, while their priming appears to be preserved.
• These findings highlight a critical immune defect in sepsis that impairs PMN effector functions.