SARS-CoV-2 Spike Protein Activates Human Lung Macrophages.

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• COVID-19, a disease caused by SARS-CoV-2, primarily affects the respiratory system.
• SARS-CoV-2 entry into host cells involves spike protein binding to ACE2 and activation by TMPRSS2.
• Human lung macrophages (HLMs) are critical immune cells in the lungs, regulating inflammation through cytokine and chemokine production.

Purpose of the Study:

• To investigate the impact of SARS-CoV-2 spike protein on HLM activation.
• To examine the expression of ACE2 and TMPRSS2 in HLMs.
• To understand the role of HLMs in COVID-19 pathogenesis.

Main Methods:

• Incubation of HLMs with purified SARS-CoV-2 spike protein.
• Measurement of cytokine and chemokine release (CXCL8, IL-6, TNF-α, IL-1β).
• Assessment of phagocytosis, intracellular calcium (Ca2+) levels, and HLM motility via microscopy.

Main Results:

• Spike protein triggered the release of pro-inflammatory cytokines (CXCL8, IL-6, TNF-α, IL-1β) from HLMs.
• Spike protein enhanced phagocytic activity and disrupted intracellular Ca2+ homeostasis in HLMs.
• HLM migration patterns were altered by spike protein exposure.
• HLMs constitutively express ACE2 and TMPRSS2 mRNA.

Conclusions:

• SARS-CoV-2 spike protein directly activates HLMs, contributing to inflammation.
• Macrophages play a significant role in COVID-19-induced lung injury and immunological dysfunction.
• Targeting macrophage activation could be a therapeutic strategy for respiratory diseases like COVID-19.