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Effect of Haemophilus influenzae type b lipopolysaccharide on complement activation and polymorphonuclear leukocyte
T J Inzana1, M F Tosi, S L Kaplan
1Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas.
Pediatric Research
|December 1, 1987
Summary
Haemophilus influenzae type b lipopolysaccharide (LPS) activates the complement system's alternative pathway and influences neutrophil functions. Hib LPS stimulates neutrophil chemiluminescence but inhibits phagocytosis, unlike Salmonella typhimurium LPS.
Area of Science:
- Immunology
- Microbiology
- Complement System
Background:
- Lipopolysaccharides (LPS) from Gram-negative bacteria are potent immune stimulants.
- Haemophilus influenzae type b (Hib) is a significant human pathogen, and its LPS role in immune interactions requires elucidation.
Purpose of the Study:
- To investigate the immunomodulatory effects of Haemophilus influenzae type b lipopolysaccharide (Hib LPS) on the human complement system and neutrophil functions.
- To compare the activity of Hib LPS with Salmonella typhimurium LPS and Salmonella minnesota Rb LPS.
Main Methods:
- Complement activation assays using human serum (normal and deficient) and specific inhibitors.
- Analysis of complement component conversion products (C3, C4, Factor B) via electrophoresis and passive hemolysis.
- Measurement of C5a activity using neutrophil shape change and aggregation.
- Assessment of neutrophil chemiluminescence and phagocytosis of opsonized bacteria.
Main Results:
- Hib LPS activated the alternative complement pathway, generating C3 degradation products.
- Hib LPS and Salmonella minnesota Rb LPS showed similar, but weaker, complement activation compared to Salmonella typhimurium LPS.
- Solubilized Hib lipid A activated the classical pathway, indicated by C4 conversion.
- Both Hib LPS and Salmonella typhimurium LPS generated similar levels of C5a activity.
- Hib LPS directly stimulated neutrophil chemiluminescence, while Salmonella typhimurium LPS did not.
- Hib LPS, its lipid A, and Salmonella minnesota Rb LPS inhibited neutrophil phagocytosis of Hib, whereas Salmonella typhimurium LPS enhanced it.
Conclusions:
- Hib LPS is a potent activator of the alternative complement pathway and modulates neutrophil functions, including chemiluminescence and phagocytosis.
- The immunomodulatory effects of Hib LPS differ from those of Salmonella typhimurium LPS, particularly regarding phagocytosis.
- Understanding these interactions is crucial for developing strategies against Hib infections.