Rapid decrease of CD16 (FcγRIII) expression on heat-shocked neutrophils and their recognition by macrophages.

Area of Science:

• Immunology
• Cellular Biology
• Inflammation Research

Background:

• Neutrophils are key innate immune cells that accumulate at inflammation sites.
• Inflammatory environments expose neutrophils to various stressors, including heat.
• Understanding neutrophil responses to stress is crucial for modulating immune responses.

Purpose of the Study:

• To investigate the effects of short, febrile-range heat stress on human peripheral blood neutrophils.
• To determine if heat-stressed neutrophils exhibit altered function and interactions with macrophages.
• To elucidate the role of heat shock protein 90 (HSP90) in mediating these heat-induced effects.

Main Methods:

• Human peripheral blood neutrophils were subjected to 90-minute heat stress at febrile-range temperatures.
• Neutrophil apoptosis was assessed.
• Interactions between heat-stressed neutrophils and human monocyte-derived macrophages (hMDMs) were studied.
• Expression of FcγRIII (CD16) on neutrophils and in supernatants was measured.
• The effect of HSP90 inhibitors on heat-stressed neutrophils was evaluated.

Main Results:

• Heat stress significantly slowed spontaneous neutrophil apoptosis.
• Heat-stressed neutrophils induced an anti-inflammatory effect in hMDMs without being engulfed.
• Cell surface FcγRIII (CD16) expression was sharply reduced, with no change in soluble CD16 levels.
• Inhibitors of HSP90 amplified the effects of heat shock on neutrophils.
• Heat stress modified neutrophil molecular patterns, preceding cell death.

Conclusions:

• Short-term febrile-range heat stress alters neutrophil function, slowing apoptosis and inducing an anti-inflammatory signal to macrophages.
• Reduced CD16 expression on heat-stressed neutrophils is a key mechanism, potentially mediated by HSP90.
• This heat-induced neutrophil modification represents a novel, early anti-inflammatory mechanism in the inflammatory response.