Cited by 80Phagocytosis and Immune RegulationImmune Response and InflammationCellular transport and secretion

Cholesterol-Rich Membrane Rafts and Lyn Are Involved in Phagocytosis during Pseudomonas aeruginosa Infection

Kannan, Shibichakravarthy, Audet, Aaron, Huang, Huang, Chen, Li-juan, Wu, Min·2008·The Journal of Immunology

Abstract

The mechanism of phagocytosis of pathogens remains to be fully characterized. We report a novel phagocytosis pathway for Pseudomonas aeruginosa, which is initiated by cholesterol-rich membrane rafts and is dependent on Lyn, primarily an immune regulator with both positive and negative roles. Blocking of Lyn or blocking of cholesterol synthesis significantly inhibited phagocytosis by alveolar macrophages. We found that Lyn, via Src homology 2 and 3 domains, bound to and then activated PI3K and Akt to regulate intracellular routing of the engulfed P. aeruginosa. Further analysis indicates that Lyn and raft components entered in phagosomes and late lysosomes. Finally, respiratory burst was dependent on Lyn and membrane rafts, as confirmed by small interfering RNA and dominant-negative strategies. Our investigations demonstrate that Lyn along with membrane rafts plays a fundamental role in phagocytosis by alveolar macrophages during infection.

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Crossref · 10.4049/jimmunol.180.4.2396

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Authors
Kannan, S., Audet, A., Huang, H., Chen, L.-J., & Wu, M.
Affiliations
  • University of North Dakota (US)
  • State Key Laboratory for Biotherapy, West China Hospital, Sichuan University , Chengdu ,
  • Sichuan University (CN)
Venue
The Journal of Immunology
Published
2008-02
Volume
180
Issue
4
Pages
2396-2408
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W1497000882
Cited by
80
References
0
Citations by year
2026: 2 · 2025: 1 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 7 · 2015: 11 · 2014: 8 · 2013: 8 · 2012: 6
FWCI
2.35
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Environmental Health Sciences (ES014690, R03ES014690)
  • National Center for Research Resources (P20RR017699)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
phagocytosis, Pseudomonas aeruginosa, Lyn kinase, alveolar macrophages, PI3K/Akt signaling, respiratory burst, phagosome maturation, bacterial infection, cholesterol biosynthesis
MeSH terms
Animals, Cells, Cultured, Cholesterol, Phagocytosis, Phagosomes, Pseudomonas Infections, Signal Transduction, Macrophages, Alveolar, Respiratory Burst, Rats, Sprague-Dawley, src-Family Kinases, Amino Acid Substitution, Membrane Microdomains, Mice, Rats

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