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.

A possible role for the ␥ subunit of immunoglobulin Fc receptors (FcR) in mucosal defenses against intestinal nematode parasites was studied using age-matched FcR␥-knockout (FcR␥ ؊/؊ ) and wild-type (FcR␥ ؉/؉ ) C57BL/6 mice. Mice were infected subcutaneously with 3,000 infective larvae of Strongyloides venezuelensis, and the degree of infection was monitored by daily fecal egg counts and adult worm recovery on days 8 and 13 postinfection. Mucosal mast cell (MMC) responses were assayed by in situ intestinal mast cell counts in stained histological sections of the jejunum and by measuring mouse mast cell protease 1 (MMCP-1) release in serum using sandwich enzyme-linked immunosorbent assay. FcR␥ ؊/؊ mice had significantly higher egg counts (P < 0.01) and numbers of adult worms (P < 0.05) than FcR␥ ؉/؉ mice, but mastocytosis and serum MMCP-1 release were comparable. It was concluded that MMCP-1 release may be spontaneous, does not depend on mast cell degranulation via the FcR␥ signaling system, and appears to play no role in the expulsion of S. venezuelensis. The delay in worm expulsion in the FcR␥ ؊/؊ mice might be related to inability of the MMC to degranulate and release effector molecules other than MMCP-1, since FcR␥ deletion abrogates mast cell degranulative responses.Fc receptors (FcR) are hetero-oligomeric complexes present on most effector cells of the immune system and, upon crosslinking by their ligand (antigen-antibody complex), mediate phagocytosis, antibody-dependent cell-mediated cytotoxicity, activation of inflammatory cells, and many other effector responses (20). However, several of the FcR require for cell surface assemblage and signal transduction into the interior of the cell an additional chain, the homodimeric ␥ subunit (20). Targeted disruption of this subunit results in pleiotropic defects in cell functions, including the loss of immunoglobulin E (IgE)-mediated mast cell degranulation (27). This is because the high-affinity FcR for IgE (FcεRI), which is also associated with host resistance to parasitic infections (12), requires the ␥ subunit to express receptor-mediated cellular functions (20). Intestinal mucosal mastocytosis is observed in certain helminth infections, and it was therefore speculated that mast cells were important in the expulsion of Strongyloides ratti in rodents (19). Subsequently, in a series of experiments in infected rodents, it was demonstrated that mucosal mast cells (MMC) induced by the mast cell growth/differentiation factor interleukin 3 (IL-3) were the effector cells in the immune expulsion of Strongyloides spp. (1,3,8,17,18). The exact mechanism of the mast cellmediated parasite expulsion is still not clear, although it has been suggested that granular contents released by activated mast cells may be the ultimate effector molecules (7, 17). Since Fc ␥ subunit deletion results in loss of mast cell function, including degranulation and granular content release (27), the aim of this study was to determine whether the MMC-mediated parasite expulsion mechanism actuall...

SUMMARY:Cadherins, calcium-dependent cell adhesion molecules, play crucial roles, not only in the maintenance of tissue integrity, but also in the regulation of many aspects of cell behavior. We investigated the expression of "classic" E-, N-and P-cadherins in bone marrow-derived cultured mast cells (BMMC) and peritoneal mast cells (PMC) from mice. Flow cytometric analysis and immunocytochemical staining indicated that E-cadherin was expressed on the cell surface of BMMC and also at lower levels on PMC. N-cadherin was also expressed on the surface of BMMC, but not of PMC, whereas P-cadherin expression was seen in neither cell type. Significant expression of E-and N-cadherin mRNA was observed in BMMC by reverse transcriptase-polymerase chain reaction (RT-PCR), but PMC expressed only E-cadherin mRNA. Western blotting analysis indicated expression of ␣-and ␤-catenins and p120-catenin (or p120 cas) in BMMC, whereas PMC showed less intense expression of ␣-and ␤-catenins with high levels of p120 expression. Analyses of ␤-catenin or E-cadherin immunoprecipitates from BMMC lysate revealed that ␣-catenin, ␤-catenin, and E-cadherin were co-precipitated, suggesting that E-cadherin and catenins form a complex in mast cells. Addition of a blocking antibody of homophilic E-cadherin interactions, or a synthetic E-cadherin-binding decapeptide containing the histidine-alanine-valine (HAV) sequence in methylcellulose cultures of gut intraepithelial mononuclear cells or BMMC, significantly suppressed the clonal growth of mast cells. Furthermore, the blocking antibody or synthetic decapeptide significantly suppressed BMMC adhesion to E-cadherin-expressing F9 cell monolayers. These results indicated that E-cadherin and associated cytoplasmic proteins in mast cells might be involved in the regulation of certain stages of mast cell differentiation and cell-cell interactions. (Lab Invest 2000, 80:1571-1581.

A rare form of sparganosis with eosinophilic pleural effusion is reported. A 62-year-old manwas admitted to our hospital with left pleural effusion, and diagnosed immunologically as having sparganosis. Eosinophilia was seen in both peripheral blood and pleural effusion. The level of interleukin (IL)-5 was elevated in the pleural effusion, but not in peripheral blood. The patient was treated successfully with three consecutive doses of praziquantel (75 mg/ kg/day). After the treatment, the antibody titer in serum decreased and the eosinophil number in the peripheral blood returned to the normal level. Thus, sparganosis should be included in the differential diagnosis for eosinophilic pleuritis. The immunoserological screening test using multiple-dot ELISA is helpful to identify the causative pathogen. (Internal Medicine 40: 783-785, 2001)

Recently several inbred strains of mice were found to be hyporesponsive to Interleukin (IL)-3 because of a 5-bp deletion in the intron 7 of the gene that encodes IL-3 receptor alpha subunit (IL-3R alpha). Due to this mutation, mast cells were not generated in vitro from bone marrow cells of these mice under the presence of IL-3. Intestinal mucosal mast cells, of which growth/differentiation is dependent on IL-3, are important effector cells in immune-mediated expulsion of intestinal nematodes, Stronglyoides spp. In the present study, therefore, we examined intestinal mast cell response and mucosal defence against Strongyloides venezuelensis in IL-3-hyporesponsive C58/J and A/J mice. After subcutaneous inoculation with 10,000 infective larvae, C58/J and IL-3-responsive C57BL/6 mice showed identical kinetic patterns of daily faecal egg output and intestinal mast cell response. When these mice were infected with 3000 L3 and, five weeks later, they were challenged by intraduodenal implantation of 800 S. venezuelensis adult worms, the timing of logarithmic decline of faecal egg count as well as intestinal mastocytosis was delayed for two days in C58/J mice. Kinetics of intestinal mastocytosis and faecal egg excretion after a primary and challenge infection in A/J mice, another IL-3-hyporesponsive strain, were identical with those seen in C58/J mice. These results suggest that intestinal mast cell response and mucosal defence against S. venezuelensis of the mutant mice were almost completely compensated in vivo. Possible mechanisms of induction of intestinal mast cell response in IL-3R alpha-defective mice are discussed.