In vitro expression of inducible nitric oxide synthase in the nasal mucosa of guinea pigs after incubation with lipopolysaccharides or cytokines.
In order to demonstrate the involvement of nitric oxide synthases (NOS)--in particular the inducible isoform (iNOS)--in inflammatory processes within the nasal airways, we used organ-bath incubation to study isolated inferior turbinates and mucosa of the maxillary sinus of guinea pigs. The pattern of the expression in various substructures of the nasal mucosa was of special interest. Mucosa was incubated for 6 h with lipopolysaccharides (LPS) produced by E. coli, interleukin II (IL-2) or tumor necrosis factor-alpha (TNF-alpha). Saline was used as the control solution. Following incubation the specimens were fixed in buffered 4% formaldehyde solution over a period of 4 h. Tissues were next exposed to nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase-reaction and immunostained with specific antibodies to iNOS. Results then showed a clearly increased or initiated expression of iNOS in epithelium, glands, leucocytes and blood vessels of treated tissues in comparison to the control specimens. The inflammatory mediator LPS and the cytokines Il-2 or TNF-alpha alone were found to be capable of increasing the expression of iNOS, although the effects of LPS clearly exceeded those of the cytokines. This finding implicates iNOS-generated nitric oxide as a key factor for causing nasal swelling, secretion and obstruction during nasal infections and allergic episodes.
Hess
A
A
Department of Oto-Rhino-Laryngology, University of Cologne, Germany.
Bloch
W
W
Rocker
J
J
Addicks
K
K
Stennert
E
E
Michel
O
O
D000818:Animals; D046508:Culture Techniques; D016207:Cytokines / Q000494:pharmacology*; D008058:Dihydrolipoamide Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D004926:Escherichia coli; D005260:Female; D006168:Guinea Pigs; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009297:Nasal Mucosa / Q000187:drug effects* / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II; D013997:Time Factors; D014420:Turbinates / Q000187:drug effects / Q000201:enzymology
D016207:Cytokines; D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D008058:Dihydrolipoamide Dehydrogenase