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 proce sses within the nasal airways, we used organ-bath incubation to study isolated inferior turbinates and mucosa of the maxillary sinus of guin ea pigs. The pattern of the expression in various substructures of the nasal mucosa was of special interest. Mucosa was incubated for 6 h wi th lipopolysaccharides (LPS) produced by E. coli, interleukin II (IL-2 ) or tumor necrosis factor-alpha (TNF-alpha). Saline was used as the c ontrol solution. Following incubation the specimens were fixed in buff ered 4% formaldehyde solution over a period of 4 h. Tissues were next exposed to nicotinamide adenine dinucleotide phosphate (NADPH)-diaphor ase-reaction and immunostained with specific antibodies to iNOS. Resul ts 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 an d the cytokines Il-2 or TNF-alpha alone were found to be capable of in creasing the expression of iNOS, although the effects of LPS clearly e xceeded those of the cytokines. This finding implicates iNOS-generated nitric oxide as a key factor for causing nasal swelling, secretion an d obstruction during nasal infections and allergic episodes.