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The fifth component of complement is not required for the clearance of Staphylococcus aureus
Abstract:
Both resident alveolar macrophages and recruited polymorphonuclear leukocytes (PMN) are required for pulmonary clearance of large inoculums of Staphylococcus aureus. We have evaluated the role of the C5 molecule in the recruitment of PMN to the lung after challenges with S. aureus using congenic C5-sufficient B10.D2/nSn (C5+) and C5-deficient B10.D2/oSn (C5-) mice. The C5+ and C5- mice were injected with water and varying inoculums of staphylococci via an endobronchial catheter. Bronchoalveolar lavage (BAL) was performed on the inoculated lung at 0 and 4 h after inoculation. Cellular response was measured and chemotactic activity was assayed in BAL supernatants at each time interval using human PMN in modified Boyden chambers by the leading front technique. Clearance of bacteria was studied by quantitative lung culture. The C5+ and C5- mice recruited similar numbers of PMN after challenges with both 10(4), 10(8), and 10(7) organisms (p = NS). The C5+ and C5- mice also generated similar amounts of chemotactic activity in BAL (p = NS). Additionally, clearance of bacteria was not impaired in C5- mice when compared with that in C5+ mice (p = NS). Our results indicate that intraalveolar chemotaxins other than C5 are of primary importance in the early recruitment of PMN after staphylococcal challenge and demonstrate that the inflammatory response within the lung is mediated by differing pathways dependent on the initiating stimulus.
Insights
Complement component 5 (C5) does not significantly impact polymorphonuclear leukocyte (PMN) recruitment or Staphylococcus aureus clearance in the lungs. Other intra-alveolar factors are crucial for early PMN response during bacterial infection.
Area of Science:
- Immunology
- Pulmonary Medicine
- Microbiology
Background:
- Pulmonary clearance of Staphylococcus aureus requires both resident alveolar macrophages and recruited polymorphonuclear leukocytes (PMN).
- The role of Complement component 5 (C5) in PMN recruitment to the lung during S. aureus infection is not fully understood.
Purpose of the Study:
- To evaluate the role of the C5 molecule in the recruitment of PMN to the lung after Staphylococcus aureus challenge.
- To compare bacterial clearance in C5-sufficient and C5-deficient mice.
Main Methods:
- Congenic C5-sufficient (B10.D2/nSn, C5+) and C5-deficient (B10.D2/oSn, C5-) mice were challenged with varying inoculums of S. aureus via endobronchial catheter.
- Bronchoalveolar lavage (BAL) was performed at 0 and 4 hours post-inoculation.
- Cellular response, chemotactic activity in BAL supernatants, and bacterial clearance via quantitative lung culture were assessed.
Main Results:
- C5+ and C5- mice exhibited similar PMN recruitment to the lung across different S. aureus inoculums (10^4, 10^7, 10^8 organisms).
- Comparable levels of chemotactic activity were observed in the BAL supernatants of both C5+ and C5- mice.
- Bacterial clearance was not impaired in C5-deficient mice compared to C5-sufficient mice.
Conclusions:
- Intra-alveolar chemotaxins, independent of C5, are primarily responsible for early PMN recruitment following S. aureus challenge.
- The inflammatory response in the lung can be mediated by distinct pathways depending on the nature of the initiating stimulus.