1. Involvement of complement pathways in patients with bacterial septicemia
- Author
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Michael Loos, Maurice G. Colomb, Chantal Dumestre-Pérard, Elke Doerr, Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), and Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)
- Subjects
MESH: Complement Pathway, Mannose-Binding Lectin ,Lipopolysaccharides ,Salmonella ,MESH: Complement C1q ,Lipopolysaccharide ,Immunology ,chemical and pharmacologic phenomena ,Bacteremia ,medicine.disease_cause ,Gram-Positive Bacteria ,Mannose-Binding Lectin ,Microbiology ,MESH: Gram-Positive Bacteria ,03 medical and health sciences ,chemistry.chemical_compound ,Classical complement pathway ,0302 clinical medicine ,medicine ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Complement Pathway, Classical ,MESH: Bacteremia ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Innate immune system ,MESH: Humans ,biology ,Complement C1q ,Lectin ,Salmonella enterica ,Complement Pathway, Mannose-Binding Lectin ,MESH: Complement Pathway, Classical ,biology.organism_classification ,bacterial infections and mycoses ,3. Good health ,Complement system ,MESH: Mannose-Binding Lectin ,chemistry ,MESH: Salmonella enterica ,Alternative complement pathway ,biology.protein ,MESH: Lipopolysaccharides ,Bacteria ,030215 immunology - Abstract
The complement system is a major humoral portion of the innate immune system, playing a significant role in host defence against microorganisms. The biological importance of this system is underlined by the fact that at least three different pathways for its activation exist, the classical, the MBL and the alternative pathway. To elucidate the involvement of the classical and/or the MBL pathway during bacterial septicemia, 32 patients with gram-positive and 30 patients with gram-negative bacterial infections were investigated. In patients with gram-positive bacteria, a significant consumption of C1q (p=0.005) but not of mannose-binding lectin (MBL) (p=0.2) was found during the acute phase of infection. In contrast, in patients with gram-negative bacterial infections, a significant reduction of MBL (p=0.002) and only a moderate, less significant reduction of C1q (p=0.03) were observed. As a model for the binding of MBL to gram-negative bacteria, Salmonella strains with defined mutations in their lipopolysaccharide (LPS) structure were used. The comparison of the binding of MBL to these Salmonella strains with that of the corresponding isolated LPS forms bound to microtiter plates revealed a similar binding pattern, supporting the interpretation that LPS on the surface of gram-negative bacteria is the major acceptor molecule for MBL on these bacteria, which according to our results obviously also takes place during gram-negative bacterial septicaemia. Furthermore, we were able to demonstrate that MBL bound to LPS was able to initiate activation of the complement cascade as measured by the occurrence of the cleavage product C4c.
- Published
- 2006