Monocyte cytokine secretion induced by chemically-defined derivatives of Klebsiella pneumoniae.
The capacity of a K. pneumoniae membrane proteoglycan (Kp-MPG) and four of its chemically defined derivatives to activate human monocytes was studied by measuring immunoreactive IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) in culture supernatants. Monocyte culture supernatants were also tested for their comitogenic activity on concanavalin A-stimulated thymocytes and for their cytotoxic activity on the mouse fibroblastic L929 cell line. The four Kp-MPG derivatives were: (i) an acylpoly(1-3)galactoside (APG); (ii) an APG preparation submitted to acid hydrolysis which removed all fatty acids but left intact the galactose chain of APG (GC-APG); (iii) a preparation obtained by mild alkaline hydrolysis, containing additional ester-linked C14 and C16 fatty acids bound to the APG molecule (EFA-APG); and (iv) a polymer of the latter compound (APG pol). Kp-MPG induced the synthesis of IL-1 beta, IL-6 and TNF-alpha with dose-responses and kinetics similar to those of Salmonella minnesota lipopolysaccharide (Sm-Re-LPS). APG pol and EFA-APG induced the secretion of the three cytokines with lower potency than Kp-MPG or Sm-Re-LPS. APG did not trigger any detectable cytokine production and GC-APG induced only borderline and inconsistent responses. Our data demonstrate the critical role of ester-linked C14 and C16 fatty acids in the triggering of monocyte response to Kp-MPG derivatives.
Hmama
Z
Z
Laboratoire d'Immunologie, INSERM U80 CNRS URA 1177 UCBL, Hôpital E. Herriot, Lyon, France.
Lina
G
G
Vincent
C
C
Wijdenes
J
J
Normier
G
G
Binz
H
H
Revillard
J P
JP
D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007711:Klebsiella pneumoniae; D008070:Lipopolysaccharides / Q000276:immunology; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D012475:Salmonella; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide