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Invasion by schistosome cercariae: studies with human skin explants
Update
TRENDS in Parasitology
Vol.19 No.8 August 2003
339
Invasion by schistosome cercariae: studies with human skin explants Phil J. Whitfield, Ann Bartlett, Marc B. Brown and Chris Marriott School of Health and Life Sciences, King’s College London, 150 Stamford St, London, UK SE1 9NN
The recent collection of articles in Trends in Parasitology on the invasion of human skin by schistosome cercariae [1 – 3] has demonstrated that, despite many decades of analysis, this crucial invasion process is not sufficiently understood. The main areas of uncertainty are: (1) the nature of the stimuli which lead to the initiation of cercarial attachment; (2) the sources of cercarial lytic enzymes at different phases of penetration (acetabular versus head gland secretions versus sub-tegumental inclusions); (3) the temporal relationship between release of proteolytic enzymes from the acetabular glands and penetration of successive tissue barriers including epidermal basement membrane; (4) the speed of penetration of skin layers and of exit from the skin; and (5) the method of entry of schistosomula into dermal blood vessels and lymphatics. There is a requirement to clarify each of these areas of imprecision. It is possible, as McKerrow has suggested [3], that some of the uncertainty arises from the multiplicity of laboratory mammal models which have been used to address experimental questions. Such mammal models are not irrelevant to transmission in the wild because many instances of natural mammalian reservoir hosts of human schistosomes have been recorded [4]. Given that the skin of model mammals, such as rats and mice, is different from human skin in relation to anatomy and physiology [5], it is important to use human skin in experiments if unambiguous data about human infection are sought. As McKerrow comments: ‘only through direct analysis of cercarial penetration of human skin explants can some of these myths be dispelled’. We agree and are surprised that McKerrow and Salter [1], Curwen and Wilson [2], and McKerrow [3] fail to cite the recent work we have published using human skin explants to further understand skin invasion by Schistosoma mansoni cercariae. Our main approach has been to use skin (obtained from cosmetic surgery patients with informed consent) held in two-chambered Franz cells. Franz cells are the pharmaceutical industry standard for assessment and optimization of drug flux across human skin in vitro. Using this method, we have defined the temporal attachment dynamics of cercariae with respect to human skin, showing that ,50% of cercariae were irreversibly attached within one minute and , 85% after 5 min [6]. Skin explants in Franz cells, as well as biopsy specimens of human foreskin, have been used to demonstrate the unexpected finding Corresponding author: Phil J. Whitfield ([email protected]). http://parasites.trends.com
that the majority of skin-penetrating S. mansoni cercariae carry their tails with them into their entry tunnels [7]. Franz cell studies with skin explants have also helped to measure the effectiveness of a dimethicone barrier cream in inhibiting cercarial skin invasion [8]. We have used this technique to test the hypothesis [9] that shared use of entry points, signalled by cercarial L-arginine secretion, enhances penetration efficiency. After five successive exposures of individual skin explants to cercariae, no such enhancement occurs [10]. Our investigations have provided new information on the contentious issue of the speed with which cercariae reach the human epidermal basement membrane. The photomicrograph in Fig. 1 from Franz cell preparations reveals a cercarial head in the dermis beneath the basement membrane within 10 min of exposure to infective larvae. These findings confirm the usefulness of direct studies with human skin when investigating cercarial invasion.
Fig. 1. Penetration of human skin by Schistosoma mansoni cercariae. Cercariae were those of an isolate (courtesy of Vaughan R. Southgate, Natural History Museum, London, UK) collected in Dagana, Senegal, and used after only two laboratory passages in snails. After exposure to cercariae (10 min), the human abdominal skin from a Franz cell preparation was stained with haemotoxylin and eosin (histological preparation kindly provided by David Joyce). The cercarial head (H) is found in a cavity within the dermis, beneath the epidermal basement membrane (M) of the skin. Scale bar ¼ 10 mm.
340
Update
TRENDS in Parasitology
Such work can complement and help to calibrate studies with model laboratory hosts. References 1 McKerrow, J.H. and Salter, J. (2002) Invasion of skin by Schistosoma cercariae. Trends Parasitol. 18, 193– 195 2 Curwen, R.S. and Wilson, R.A. (2003) Invasion of skin by schistosome cercariae: some neglected facts. Trends Parasitol. 19, 63 – 66 3 McKerrow, J.H. (2003) Invasion of skin by schistosome cercariae: some neglected facts. Trends Parasitol. 19, 66 – 68 4 Duplantier, J.M. and Sene, M. (2000) Rodents as reservoir hosts in the transmission of Schistosoma mansoni in Richard-Toll, Senegal, West Africa. J. Helminthol. 74, 129 – 135 5 Monteiro-Riviere, N.A. (1996) Anatomical factors affecting barrier function in ‘Dermatotoxicology’, (Murzulli, F.N. and Maibach, H.I. eds.), pp. 3 – 18, Taylor and Francis, London
Vol.19 No.8 August 2003
6 Bartlett, A. et al. (2000) The infection of human skin by schistosome cercariae: studies using Franz cells. Parasitology 121, 49 – 54 7 Whitfield, P.J. et al. (2003) Delayed tail loss during the invasion of human skin by schistosome cercariae. Parasitology 126, 135– 140 8 Ingram, R.J. et al. (2002) Dimethicone barrier cream prevents infection of human skin by schistosome cercariae: evidence from Franz cell studies. J. Parasitol. 88, 399– 402 9 Haas, W. (1994) Physiological analysis of host-finding behaviour in trematode cercariae: adaptations for transmission success. Parasitology 109, S15– S29 10 Ingram, R.J. et al. (2003) Penetration of human skin by the cercariae of Schistosoma mansoni: an investigation of the effect of multiple cercarial applications. J. Helminthol. 77, 27– 31
1471-4922/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S1471-4922(03)00143-0
Endeavour the quarterly magazine for the history and philosophy of science Online access to Endeavour is FREE to BioMedNet subscribers, providing you with a collection of beautifully illustrated articles on the history of science, book reviews and editorial comment.
featuring The pathway to the cell and its organelles: one hundred years of the Golgi apparatus by M. Bentivoglio and P. Mazzarello Joseph Fourier, the ‘greenhouse effect’ and the quest for a universal theory of terrestrial temperatures by J.R. Fleming The hunt for red elixir: an early collaboration between fellows of the Royal Society by D.R. Dickson Art as science: scientific illustration 1490–1670 in drawing, woodcut and copper plate by C.M. Pyle The history of reductionism versus holistic approaches to scientific research by H. Andersen Reading and writing the Book of Nature: Jan Swammerdam (1637–1680) by M. Cobb Coming to terms with ambiguity in science: wave–particle duality by B.K. Stepansky The role of museums in history of science, technology and medicine by L. Taub The ‘internal clocks’ of circadian and interval timing by S. Hinton and W.H. Meck The troubled past and uncertain future of group selectionism by T. Shanahan A botanist for a continent: Ferdinand Von Mueller (1825–1896) by R.W. Home Rudolf Virchow and the scientific approach to medicine by L. Benaroyo Darwinism and atheism: different sides of the same coin? by M. Ruse Alfred Russel Wallace and the flat earth controversy by C. Garwood John Dalton: the world’s first stereochemist by Dennis H. Rouvray Forensic chemistry in 19th-century Britain by N.G. Coley Owen and Huxley: unfinished business by C.U.M. Smith Characteristics of scientific revolutions by H. Andersen and much, much more . . . Locate Endeavour in the BioMedNet Reviews collection. Log on to http://reviews.bmn.com, hit the ‘Browse Journals’ tab and scroll down to Endeavour http://parasites.trends.com
TRENDS in Parasitology
Vol.19 No.8 August 2003
339
Invasion by schistosome cercariae: studies with human skin explants Phil J. Whitfield, Ann Bartlett, Marc B. Brown and Chris Marriott School of Health and Life Sciences, King’s College London, 150 Stamford St, London, UK SE1 9NN
The recent collection of articles in Trends in Parasitology on the invasion of human skin by schistosome cercariae [1 – 3] has demonstrated that, despite many decades of analysis, this crucial invasion process is not sufficiently understood. The main areas of uncertainty are: (1) the nature of the stimuli which lead to the initiation of cercarial attachment; (2) the sources of cercarial lytic enzymes at different phases of penetration (acetabular versus head gland secretions versus sub-tegumental inclusions); (3) the temporal relationship between release of proteolytic enzymes from the acetabular glands and penetration of successive tissue barriers including epidermal basement membrane; (4) the speed of penetration of skin layers and of exit from the skin; and (5) the method of entry of schistosomula into dermal blood vessels and lymphatics. There is a requirement to clarify each of these areas of imprecision. It is possible, as McKerrow has suggested [3], that some of the uncertainty arises from the multiplicity of laboratory mammal models which have been used to address experimental questions. Such mammal models are not irrelevant to transmission in the wild because many instances of natural mammalian reservoir hosts of human schistosomes have been recorded [4]. Given that the skin of model mammals, such as rats and mice, is different from human skin in relation to anatomy and physiology [5], it is important to use human skin in experiments if unambiguous data about human infection are sought. As McKerrow comments: ‘only through direct analysis of cercarial penetration of human skin explants can some of these myths be dispelled’. We agree and are surprised that McKerrow and Salter [1], Curwen and Wilson [2], and McKerrow [3] fail to cite the recent work we have published using human skin explants to further understand skin invasion by Schistosoma mansoni cercariae. Our main approach has been to use skin (obtained from cosmetic surgery patients with informed consent) held in two-chambered Franz cells. Franz cells are the pharmaceutical industry standard for assessment and optimization of drug flux across human skin in vitro. Using this method, we have defined the temporal attachment dynamics of cercariae with respect to human skin, showing that ,50% of cercariae were irreversibly attached within one minute and , 85% after 5 min [6]. Skin explants in Franz cells, as well as biopsy specimens of human foreskin, have been used to demonstrate the unexpected finding Corresponding author: Phil J. Whitfield ([email protected]). http://parasites.trends.com
that the majority of skin-penetrating S. mansoni cercariae carry their tails with them into their entry tunnels [7]. Franz cell studies with skin explants have also helped to measure the effectiveness of a dimethicone barrier cream in inhibiting cercarial skin invasion [8]. We have used this technique to test the hypothesis [9] that shared use of entry points, signalled by cercarial L-arginine secretion, enhances penetration efficiency. After five successive exposures of individual skin explants to cercariae, no such enhancement occurs [10]. Our investigations have provided new information on the contentious issue of the speed with which cercariae reach the human epidermal basement membrane. The photomicrograph in Fig. 1 from Franz cell preparations reveals a cercarial head in the dermis beneath the basement membrane within 10 min of exposure to infective larvae. These findings confirm the usefulness of direct studies with human skin when investigating cercarial invasion.
Fig. 1. Penetration of human skin by Schistosoma mansoni cercariae. Cercariae were those of an isolate (courtesy of Vaughan R. Southgate, Natural History Museum, London, UK) collected in Dagana, Senegal, and used after only two laboratory passages in snails. After exposure to cercariae (10 min), the human abdominal skin from a Franz cell preparation was stained with haemotoxylin and eosin (histological preparation kindly provided by David Joyce). The cercarial head (H) is found in a cavity within the dermis, beneath the epidermal basement membrane (M) of the skin. Scale bar ¼ 10 mm.
340
Update
TRENDS in Parasitology
Such work can complement and help to calibrate studies with model laboratory hosts. References 1 McKerrow, J.H. and Salter, J. (2002) Invasion of skin by Schistosoma cercariae. Trends Parasitol. 18, 193– 195 2 Curwen, R.S. and Wilson, R.A. (2003) Invasion of skin by schistosome cercariae: some neglected facts. Trends Parasitol. 19, 63 – 66 3 McKerrow, J.H. (2003) Invasion of skin by schistosome cercariae: some neglected facts. Trends Parasitol. 19, 66 – 68 4 Duplantier, J.M. and Sene, M. (2000) Rodents as reservoir hosts in the transmission of Schistosoma mansoni in Richard-Toll, Senegal, West Africa. J. Helminthol. 74, 129 – 135 5 Monteiro-Riviere, N.A. (1996) Anatomical factors affecting barrier function in ‘Dermatotoxicology’, (Murzulli, F.N. and Maibach, H.I. eds.), pp. 3 – 18, Taylor and Francis, London
Vol.19 No.8 August 2003
6 Bartlett, A. et al. (2000) The infection of human skin by schistosome cercariae: studies using Franz cells. Parasitology 121, 49 – 54 7 Whitfield, P.J. et al. (2003) Delayed tail loss during the invasion of human skin by schistosome cercariae. Parasitology 126, 135– 140 8 Ingram, R.J. et al. (2002) Dimethicone barrier cream prevents infection of human skin by schistosome cercariae: evidence from Franz cell studies. J. Parasitol. 88, 399– 402 9 Haas, W. (1994) Physiological analysis of host-finding behaviour in trematode cercariae: adaptations for transmission success. Parasitology 109, S15– S29 10 Ingram, R.J. et al. (2003) Penetration of human skin by the cercariae of Schistosoma mansoni: an investigation of the effect of multiple cercarial applications. J. Helminthol. 77, 27– 31
1471-4922/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S1471-4922(03)00143-0
Endeavour the quarterly magazine for the history and philosophy of science Online access to Endeavour is FREE to BioMedNet subscribers, providing you with a collection of beautifully illustrated articles on the history of science, book reviews and editorial comment.
featuring The pathway to the cell and its organelles: one hundred years of the Golgi apparatus by M. Bentivoglio and P. Mazzarello Joseph Fourier, the ‘greenhouse effect’ and the quest for a universal theory of terrestrial temperatures by J.R. Fleming The hunt for red elixir: an early collaboration between fellows of the Royal Society by D.R. Dickson Art as science: scientific illustration 1490–1670 in drawing, woodcut and copper plate by C.M. Pyle The history of reductionism versus holistic approaches to scientific research by H. Andersen Reading and writing the Book of Nature: Jan Swammerdam (1637–1680) by M. Cobb Coming to terms with ambiguity in science: wave–particle duality by B.K. Stepansky The role of museums in history of science, technology and medicine by L. Taub The ‘internal clocks’ of circadian and interval timing by S. Hinton and W.H. Meck The troubled past and uncertain future of group selectionism by T. Shanahan A botanist for a continent: Ferdinand Von Mueller (1825–1896) by R.W. Home Rudolf Virchow and the scientific approach to medicine by L. Benaroyo Darwinism and atheism: different sides of the same coin? by M. Ruse Alfred Russel Wallace and the flat earth controversy by C. Garwood John Dalton: the world’s first stereochemist by Dennis H. Rouvray Forensic chemistry in 19th-century Britain by N.G. Coley Owen and Huxley: unfinished business by C.U.M. Smith Characteristics of scientific revolutions by H. Andersen and much, much more . . . Locate Endeavour in the BioMedNet Reviews collection. Log on to http://reviews.bmn.com, hit the ‘Browse Journals’ tab and scroll down to Endeavour http://parasites.trends.com