Abe T et al. (1987) Parasite Immunol "Localization of mucosal mast cells in W/Wv mice after reconstitution with bone marrow cells or cultured mast cells, and its relation to the protective capacity to Strongyloides ratti infection."

Nawa Y, Abe T

[Parasite Immunol, 1987]

Localization of mast cells in the intestinal epithelium, villous lamina propria and basal lamina propria of mast cell-deficient WBB6F1 (W/Wv) mice reconstituted with either bone marrow cells or with cultured mast cells (BMMC) was compared to that of mast cell-sufficient C57BL/6 or C57BL/6-bgj/bgj (beige) mice after infection with Strongyloides ratti. In mast cell-sufficient C57BL/6 or beige mice, the maximum number of intestinal mucosal mast cells (MMC) was more than 160 MMC/10 villus crypt units (VCU) and more than 90% of MMC were located in the intestinal epithelium. When W/Wv mice were reconstituted with bone marrow cells of beige mice, worm expulsion was hastened and the MMC response became comparable to that of mast cell-sufficient mice in terms of cell numbers and their intra-epithelial localization. On the other hand, when W/Wv mice were reconstituted with BMMC of beige mice, only a few donor type MMC were detected in the intestine. The proportion of intra-epithelial MMC was lower than that of mast cell-sufficient mice or of marrow-reconstituted W/Wv mice. Even repeated injection of BMMC could not fully restore the number of intra-epithelial MMC to the level of that observed in mast cell-sufficient mice. Since mast cell-growth factor-producing activity of W/Wv mice was comparable to that of mast cell-sufficient mice, the ineffectiveness of BMMC-transfer in restoring protective activity or MMC responses in W/Wv mice seems to be attributed to the functional immaturity or inactivity of BMMC.

Wildenburg G et al. (1998) Trop Med Int Health "Ivermectin influence on the mast cell activity in nodules of onchocerciasis patients."

Mainuka P, Buttner DW, Wildenburg G, Korten S

[Trop Med Int Health, 1998]

Onchocercal nodules were stained immunohistochemically using antibodies specific for human mast cells and IgE to elucidate the localization and frequency of mast cells after a single oral dose of 150 microg/kg ivermectin. Tryptase-and chymase-positive mast cells occurred predominantly in mixed inflammatory infiltrates and perivascularly, and never adhered to adult worms or microfilariae. Up to three days after ivermectin, mast cells and IgE-positive cells were markedly increased in the capsular area of nodules containing female worms with embryos and microfilariae compared to untreated nodules. In the centre of these nodules, around the adult Onchocerca volvulus, we found many tryptase-positive cells. More mast cells were IgE-positive than in untreated nodules, equalling the number of tryptase-positive mast cells. There was a clear correlation between the appearance of mast cells and the attacks on damaged microfilariae by eosinophils and macrophages and in the vicinity of adult worms by neutrophils that occur soon after ivermectin treatment. Onchocercomata harbouring female worms with oocytes only revealed, after all treatment intervals, the same mast cell numbers as untreated nodules. In conclusion, during the first three days after administration, ivermectin produces increased numbers of mast cells in nodules harbouring females with embryos and microfilariae, probably as part of an allergic reaction to the attacked microfilariae. Four to 19 days after ivermectin the number of mast cells in the entire nodule is no longer elevated.

Olson CE et al. (1978) Am J Trop Med Hyg "Strongyloides ratti infections in rats. I. Immunopathology."

Schiller EL, Olson CE

[Am J Trop Med Hyg, 1978]

The elimination of adult parasites from the intestines of rats after a first and second infection of Strongyloides ratti was studied. Expulsion after a second infection was anamnestic, indication that the response is immunologic. Intestinal mast cell responses accompanied damage and expulsion of worms, the secondary mast cell response being more rapid but less intense that the first. Antithymocyte serum suppressed expulsion as well as both the intestinal mast cell and circulating eosinophil responses to primary infection.

Watanabe K et al. (2009) Parasite "Strongyloides ratti: implication of mast cell-mediated expulsion through FcepsilonRI-independent mechanisms."

Tada I, Nomoto K, Hamano S, Kishihara K, Watanabe K, Koga M

[Parasite, 2009]

In order to examine whether FcepsilonRI-dependent degranulation of intestinal mast cells is required for expulsion of intestinal nematode Strongyloides ratti, CD45 exon6-deficient (CD45-/-) mice were inoculated with S. ratti. In CD45-/- mice, egg excretion in feces persisted for more than 30 days following S. ratti larvae inoculation, whereas in wild-type (CD45+/+) mice, the eggs completely disappeared by day 20 post-infection. The number of intestinal mucosal mast cells, which are known effector cells for the expulsion of S. ratti, was 75% lower in CD45-/- mice compared with that in CD45+/+ mice. Adoptive transfer of wild-type T cells from CD45+/+ mice into CD45-/- mice reduced the duration of S. ratti infection to comparable levels observed in CD45+/+ mice, with concomitant increases in intestinal mucosal mast cells. These results showed that CD45 is not involved in the effector function of intestinal mucosal mast cells against S. ratti infection. Since FcepsilonRI-dependent degranulation of mast cells is completely impaired in these CD45 knockout mice, we conclude that FcepsilonRI-dependent degranulation is not required in the protective function of intestinal mucosal mast cells against primary infection of S. ratti.

Abe T et al. (1987) Parasite Immunol "Reconstitution of mucosal mast cells in W/WV mice by adoptive transfer of bone marrow-derived cultured mast cells and its effects on the protective capacity to Strongyloides ratti-infection."

Abe T, Nawa Y

[Parasite Immunol, 1987]

Bone marrow-derived cultured mast cells (BMMC) were transferred intravenously into W/WV mice to examine if they could reconstitute defective mucosal mast cell response or defective protective capacity against infection with Strongyloides ratti. When mast cell growth factor-producing activity of W/WV mice were examined, mesenteric lymph node cells obtained at 7 to 14 days after infection could produce this factor in vitro by stimulation with S. ratti-adult worm antigen. A single injection of BMMC (1 X 10(7] on day 7 post-infection (p.i.) neither caused an increase in number of intestinal mucosal mast cells not altered the kinetics of faecal larval output (LPG). On the other hand, serial injections of BMMC (5 X 10(6] from day 5 to 10 p.i. (total 3 X 10(7) cells) resulted in the significant increase in number of intestinal mucosal mast cells. However, this treatment too could not alter the kinetics of LPG. Therefore, adoptive transfer of BMMC could cause the increase in number of histologically detectable-mucosal mast cells, but these cells are, by themselves, not sufficient to cause the expulsion of S. ratti adult worms from the intestine.

Korten S et al. (1998) Acta Trop "Mast cells in onchocercomas from patients with hyperreactive onchocerciasis (sowda)."

Korten S, Buttner DW, Wildenburg G, Darge K

[Acta Trop, 1998]

In onchocerciasis, variations of the host's immune responsiveness produce a spectrum of clinical manifestations ranging from the common generalized to the rare hyperreactive form (sowda). For further characterization of the immune response, the localization and frequency of mast cells in onchocercomas from untreated and ivermectin-treated patients with hyperreactive onchocerciasis from Liberia and the Yemen were analysed and compared to the generalized form by immunohistochemistry with antibodies specific for human mast cell tryptase and chymase, histamine and IgE. The nodules were selected with special regard to only one pair of live, microfilariae-producing Onchocerca volvulus. Throughout the nodular tissue of the hyperreactive form, mast cells accumulated in the strong inflammatory infiltrates, especially near eosinophils and around cellular attacks on microfilariae as well as perivascularly. Their number was significantly higher in the whole nodular tissue compared to the generalized form. The highest numbers occurred in the nodule centre. Mast cells carried IgE and appeared activated. No mast cells were observed in the cystic parts or attached to adult worms or microfilariae. In onchocercomas, 1 and 3 days after treatment with ivermectin, microgranuloma formation by eosinophils and macrophages around damaged microfilariae was enhanced and accompanied by numerous mast cells. Attacks of neutrophils were also pronounced, but attacks by mast cells were not observed. In conclusion, hyperreactivity against microfilariae in onchocercomas clearly correlates with a strong mastocytosis and IgE production parallel to tissue eosinophilia.

Maiato H et al. (2002) J Cell Biol "MAST/Orbit has a role in microtubule-kinetochore attachment and is essential for chromosome alignment and maintenance of spindle bipolarity."

Sampaio P, Lemos CL, Carmena M, Maiato H, Earnshaw WC, Sunkel CE, Findlay J

[J Cell Biol, 2002]

Multiple asters (MAST)/Orbit is a member of a new family of nonmotor microtubule-associated proteins that has been previously shown to be required for the organization of the mitotic spindle. Here we provide evidence that MAST/Orbit is required for functional kinetochore attachment, chromosome congression, and the maintenance of spindle bipolarity. In vivo analysis of Drosophila mast mutant embryos undergoing early mitotic divisions revealed that chromosomes are unable to reach a stable metaphase alignment and that bipolar spindles collapse as centrosomes move progressively closer toward the cell center and eventually organize into a monopolar configuration. Similarly, soon after depletion of MAST/Orbit in Drosophila S2 cells by double-stranded RNA interference, cells are unable to form a metaphase plate and instead assemble monopolar spindles with chromosomes localized close to the center of the aster. In these cells, kinetochores either fail to achieve end-on attachment or are associated with short microtubules. Remarkably, when microtubule dynamics is suppressed in MAST-depleted cells, chromosomes localize at the periphery of the monopolar aster associated with the plus ends of well-defined microtubule bundles. Furthermore, in these cells, dynein and ZW10 accumulate at kinetochores and fail to transfer to microtubules. However, loss of MAST/Orbit does not affect the kinetochore localization of D-CLIP-190. Together, these results strongly support the conclusion that MAST/Orbit is required for microtubules to form functional attachments to kinetochores and to maintain spindle bipolarity.

Muralidhara P et al. (1996) Indian J Med Res "Role of calcium influx & energy metabolism in histamine release by filarial antigen in Mastomys natalensis experimentally infected with Brugia malayi."

Mahajan RC, Malla N, Muralidhara P, Ganguly NK

[Indian J Med Res, 1996]

The present work was undertaken to study the biochemical pathways involved in terms of role of calcium influx and status of energy metabolism in the activation of mast cells obtained from Mastomys natalensis infected with Brugia malayi when challenged in vitro with a potentially allergenic antigen (60 kDa) of Brugia malayi. It was observed that histamine release from sensitized lung and peritoneal mast cells was associated with intracellular influx of radioactive Ca2+, thus establishing the role of calcium in histamine release. The process of activation of mast cells by 60 kDA antigen was an energy requiring process as it utilized the energy phosphates in the form of ATP and the cells followed the aerobic respiratory pathway for the generation of energy molecules.

Watanabe K et al. (2001) Parasitol Res "The effect of interleukin-4 on the induction of intestinal mast cells and chronological cytokine profiles during intestinal nematode Strongyloides ratti infection."

Noda K, Yada S, Nomoto K, Hamano S, Tada I, Watanabe K, Kishihara K

[Parasitol Res, 2001]

The effect of interleukin-4 (IL-4) on the induction of intestinal mast cells and cytokine profiles during Strongyloides ratti infection was studied using IL-4 knockout (IL-4 KO) mice. The antigen-specific proliferative response of mesenteric lymph node cells was not impaired in IL-4 KO mice. The number of intestinal mast cells induced in IL-4 KO mice during S. ratti infection was 2- to 3-fold lower than that observed in WT mice. Intestinal mastocytosis had disappeared in IL-4 KO mice by day 21 postinfection, when significant mastocytosis continued to be observed in WT mice. In mesenteric lymphnode of IL-4 KO, IL-3 production decreased and mice IFN-gamma production significantly increased as compared with those of WT mice. The numbers of eggs excreted per gram of feces (EPG) by IL-4 KO mice were greater than those excreted by WT mice on day 6 postinfection, but no difference was observed in the subsequent period. In conclusion, intestinal mast cells are induced during S. ratti infection in the absence of IL-4, and IL-4 is not essential for protection against intestinal adult worms of S. ratti.

Abe T et al. (1988) Parasitol Res "Kinetic study of mast-cell growth factor production by lymphocytes during the course of Strongyloides ratti infection in mice."

Nawa Y, Abe T

[Parasitol Res, 1988]

Mast-cell growth factor (MCGF) activity in the media conditioned by mesenteric lymph node or spleen cells from Strongyloides ratti-infected C57BL/6 mice was examined by using factor-dependent cell line FDC-P2 or bone marrow-derived, cultured mast cells (BMMC) as indicators. Mesenteric lymph node cells from infected mice spontaneously released MCGF activity by culturing for 24 h, showing peak production on days 5-7. MCGF production by mesenteric lymph node cells was augmented after stimulation with adult worm antigen or with concanavalin A (con A). The peak of MCGF production by antigen-stimulated lymph node cells was observed on days 5-7 and declined thereafter. MCGF production by antigen-stimulated spleen cells was lower than that by lymph node cells and reached a peak on day 7 or later. Normal lymph node or spleen cells did not produce MCGF activity even after stimulation with adult worm antigen. The peak of MCGF production by mesenteric lymph node cells preceded the peak of intestinal mastocytosis at the infected site by 4-6 days. The cells producing MCGF had a phenotype of Thy-1+, L3T4+, and Lyt-2-. The possible importance of mucosal mast cells in worm expulsion is discussed.