ICAM-1 AND INOS EXPRESSION INCREASED IN THE SKIN OF MICE AFTER VACCINATION WITH GAMMA-IRRADIATED CERCARIAE OF SCHISTOSOMA-MANSONI

Host responses to migrating schistosomula of Schistosoma mansoni were compared in the sl;in of naive, multiply infected, or vaccinated (with gamma-irradiated cercariae) mice during the first 72 br after cercari al penetration. Cellular response to the migrating parasite was minima l in the skin of naive mid for up to 72 hr after infection. In sharp c ontrast, the multiply infected or vaccinated animals exhibited a marke d inflammatory response in the skin as early as 8 hr after cutaneous p enetration of the challenge cercariae. This early inflammatory respons e in the skin of sensitized animals was characterized bq; a significan t increase in the number of infiltrating cells, predominantly mononucl ear cells and neutrophils. Increased exudation of serum proteins was a lso present in the skin of sensitized animals in areas of cercarial ch allenge. A rime course of analyses revealed that mononuclear cell numb ers increased significantly in the skin of vaccinated animals as early as 60 min after a challenge infection and continued to be present at a significantly higher level up ro 72 hr after challenge, Peak neutrop hil responses occurred in the skin at 24 hr (in multiply infected anim als) and at 48 hr (in vaccinated animals) after a challenge infection. Along with the massive cellular infiltration there was an increased t issue expression of ICAM-1 and mRNA for iNOS in the skin of sensitized animals. Further analysis showed that in sensitized animals increased ICAM-1 expression was predominantly found on endothelial cells lining dermal capillaries, especially in areas around schistosomular migrati on and on cells that surrounded schistosomula in the dermis, In naive animals, however, a similar infection did not induce any ICAM-1 expres sion or iNOS production in the skin. Thus, an ICAM-1-mediated early ac cumulation of mononuclear cells in the skin and local production of ni tric oxide may be important for the initial cutaneous inflammatory/Imm une responses to migrating schistosomula of S. mansoni in vaccinated a nimals. On the contrary, in naive animals a potential parasite-induced suppression of ICAM-1 may play an important role in reducing cellular reaction in the skin and consequently help the parasite evade immune responses in the skin. (C) 1997 Academic Press.