Experimental and Clinical Studies of SLPI, with Special Reference to IgE-Mediated Allergic Reactions

Sammanfattning: In this study we demonstrated the production of SLPI (Secretory Leukocyte Protease Inhibitor) in serous glands in the nasal mucosa. We have shown that the pattern of the expression of mRNA corresponds to the encoded protein. The encoded protein was detected by immunohistochemical methods and mRNA was discovered by in situ hybridisation. Nasal mucosa from 11 test subjects without atopic disposition was used for this in vitro study. We found that SLPI inhibits IgE mediated histamine release in a dose dependent way. SLPI had no influence on spontaneous histamine release. Double-immunolabelling revealed that SLPI coexists with tryptase and chymase in tonsilar mast cells. The proportion SLPI/tryptase was 60% and the proportion SLPI/chymase was 37%. SLPI was found in 31% of these cells. In situ hybridisation detected SLPI mRNA in all mast cells. In situ hybridisation was performed as a double immunostaining, using a mouse anti-human mast cell antibody as mast cell identification. Mast cells in nasal mucosa also showed immunoreactivity for SLPI. We investigated the role of SLPI in patients with allergic rhinitis. From this point of view, we also examined leokocyte elastase, a1- PI and albumin. We used the method of unilateral antigen challenge. There was a higher level of SLPI in lavage fluid from healthy subjects than from atopic patients. SLPI increased in response to allergen challenged in atopics but not in healthy subjects. SLPI also increased in the non challenged left nostril, indicating that neural reflexes are involved in the SLPI-release. There was a higher concentration of elastase, a1-PI and albumin before antigen challenge in atopics patients out of pollen season than in healthy subjects. An increase in elastase, a1-PI and albumin was seen in the right challenged nostril, but not in the left non-challenged side exclusively in the atopic subjects. An irrelevant antigen did not increase the secretion of SLPI, elastase, a1- PI and albumin in atopic or healthy subjects.