Hisamitsu Ide

Selective effector mechanisms for the expulsion of intestinal helminths

In the middle of the era of molecular biology, much less attention is paid to in vivo phenomena. However, carefully designed experimental systems in vivo still can provide valuable information as to the mechanisms underlying the establishment and maintenance of host‐parasite relationships. In this review we describe the advantage of using concurrent infections with appropriately chosen combinations of different genera or different maturation stages of parasites to segregate the cellular responses of the host. By means of simple experimental approaches we have found that mucosal mast cells and goblet cells, both of which have long been considered as non‐specific effectors, are in fact highly selective and specific effector cells of the host defence mechanisms capable of acting on the establishment and the expulsion of intestinal helminths.

Goblet cell mucins of four genera of the subfamily Cricetinae with reference to the protective activity against Strongyloides venezuelensis

Goblet and mast cell responses in the jejunum of four genera, Mesocricetus auratus (Syrian hamster), Phodopus campbelli, Cricetulus griseus (Chinese hamster), and Tscherskia triton, belonging to the subfamily Cricetinae, were examined after infection with Strongyloides venezuelensis. Parasite eggs became detectable in faeces of all four genera on Day 7. Faecal egg count peaked around Day 8 in C. griseus and T. triton and around Day 14 in M. auratus and P. campbelli. In M. auratus and P. campbelli, faecal egg production persisted over 40 days, whereas that in C. griseus and T. triton rapidly terminated within 14 days. In all four genera examined, goblet cell hyperplasia and mastocytosis were observed at the time of expulsion of S. venezuelensis. However, in the comparative study of all four genera, neither the degree of goblet or mast cell hyperplasia nor the phenotype of mast cells correlated to the rapidity of the expulsion of S. venezuelensis. On the other hand, the rapidity of expulsion closely correlated with the degree of sulphation of goblet cell mucins because two genera, C. griseus and T. triton, having highly sulphated goblet cell mucins showed faster expulsion of S. venezuelensis than the other two genera, P. campbelli and M. auratus, having less sulphated mucins. These results suggest that physicochemical nature of mucins is critical for the expulsion of S. venezuelensis from the subfamily Cricetinae.

Immunohistochemical demonstration of inter-alpha-trypsin inhibitor light chain (bikunin) in human mast cells.

Abstract We recently reported that the rat mast cell proteinase inhibitor trypstatin is genetically identical with the second half of inter-α-trypsin inhibitor light chain (ITI-LC), also known as bikunin or urinary trypsin inhibitor (UTI). In this study, therefore, immunoreactivities of mast cells of various human tissues were examined with three antibodies, anti-human ITI-LC, anti-ITI, which recognizes mainly heavy chains or the sugar moiety of ITI, and anti-α 1-microglobulin (α1mG). ITI-LC immunoreactivity was strongly found in mast cells in the connective tissues of various organs except for those of the propria mucosae of small intestine. Neither anti-ITI antibody nor anti-α1mG antibody reacted with mast cells in various tissues. By reverse transcription-polymerase chain reaction (RT-PCR) analysis, α1mG/ITI-LC mRNA was not detected in the skin and tongue, and only weakly in small intestine, although ITI-LC immunoreactivity was strongly detected in these tissues. Furthermore, the mRNA was not expressed in cultured human mast cells. These results suggest that ITI-LC protein is stored in the granules of human connective tissue mast cells, though is not produced by them.

Sequencing of cDNAs encoding α1-microglobulin/bikunin of Mongolian gerbil and Syrian golden hamster in comparison with man and other species

Complementary DNAs (cDNAs) encoding alpha 1-microglobulin (alpha 1mG)/bikunin, also known as inter-alpha-inhibitor (I alpha I) light chain, were cloned from liver extracts of the Mongolian gerbil, Meriones unguiculatus, and the Syrian golden hamster, Mesocricetus auratus, by reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends methods. From the deduced amino-acid sequences of alpha 1mG/bikunin of gerbil and hamster, the basic molecular structure of the proteins seemed to be well-conserved. However, near the proposed sequence of proteinase inhibitory sites of two Kunitz domains in the bikunin part, variable regions composed of three amino acids each were observed between species, including rodents. Since the second half of bikunin is genetically identical with the mast cell proteinase inhibitor, trypstatin, the bikunin of each animal may have distinct inhibitory activity against mast cell proteinases.