Abe T et al. (1993) Immunology "Intestinal protection against Strongyloides ratti and mastocytosis induced by administration of interleukin-3 in mice."

Ishida K, Abe T, Sugaya H, Tasdemir I, Khan WI, Yoshimura K

[Immunology, 1993]

Information about interleukin-3 (IL-3) effects in vivo is limited compared with the in vitro effects. We found that a repetitive injection of a low dose of recombinant IL-3 induced protection against intestinal worms of Strongyloides ratti in C57BL/6 mice. When mice were injected i.p. with different doses of recombinant IL-3 twice a day from day -5 to day -1 and infected orally with larvae recovered from the head of infected rats on day 0, worm recovery from the small intestine was markedly reduced by a total of 10(4) U IL-3 or more on day 2 post-infection. The number of intestinal mucosal mast cells (MMC) was increased by the protective dose of IL-3. The IL-3 treatment, however, was ineffective in protecting mice against tissue migrating larvae, as assessed by recovery from the head. The protective effect of IL-3 on intestinal worms was observed within 6 hr post oral infection, suggesting little concern with antigen-specific immune responses. The effective dose of IL-3 treatment increased the number of MMC progenitors five times in the spleen and the mesenteric lymph nodes. An MMC-specific protease, MMCP-1, was secreted 200 times more than in controls in the intestinal lumen by the IL-3 treatment. The IL-3 treatment induced no protection or mastocytosis in mast cell-deficient W/Wv mice. These results suggest that the IL-3-induced intestinal protection against S. ratti is mediated by MMC.

Abe T et al. (1992) Immunology "Induction of the expulsion of Strongyloides ratti and retention of Nippostrongylus brasiliensis in athymic nude mice by repetitive administration of recombinant interleukin-3."

Nawa Y, Abe T, Yoshimura K, Sugaya H

[Immunology, 1992]

A repetitive administration of recombinant interleukin-3 (rIL-3), which can induce the expulsion of Strongyloides ratti in athymic nude mice, did not affect the expulsion of Nippostrongylus brasiliensis. Nude mice infected with N. brasiliensis were injected i.p. with a total of 6.8 x 10(5) U rIL-3 or medium twice a day from Day 5 to Day 11 post-infection. The kinetics of expulsion estimated by egg excretion in faeces up to Day 20 post-infection and adult worm burden on Day 21 was not affected by the IL-3 administration. A similar administration with a higher dose (total 10.6 x 10(5) U) of rIL-3 did not alter the adult worm burden on Day 13. The number of intestinal mucosal mast cells on Day 13 was markedly increased by the treatment, although the number of intestinal goblet cells was comparable between the treated and control mice. When nude mice were infected concurrently with N. brasiliensis and S. ratti and then injected repeatedly with rIL-3 (total 2.2 x 10(5) U) from Day 5 to Day 11, adult worms of S. ratti were expelled from the small intestine by Day 13; however adult worms of N. brasiliensis were retained. Again in the concurrent infection, the number of intestinal mucosal mast cells was significantly increased but that of intestinal goblet cells was not altered by the rIL-3 administration. These results indicate that the expulsion of S. ratti is dependent on IL-3 whereas that of N. brasiliensis is less dependent on IL-3.

Abe T et al. (1988) Immunology "Worm expulsion and mucosal mast cell response induced by repetitive IL-3 administration in Strongyloides ratti-infected nude mice."

Abe T, Nawa Y

[Immunology, 1988]

After a primary infection of congenitally athymic nu/nu mice with Strongyloides ratti, worms were not expelled and the number of intestinal mucosal mast cells (MMC) remained at a low level. When S. ratti-infected nu/nu mice were treated by repetitive injections of semi-purified IL-3 from Day 5 to Day 10 post-infection (total 1.4 X 10(5) U), significant reduction of larval excretion in faeces (LPG) was observed on Day 13. The number of adult worms in the small intestine of IL-3-treated mice was significantly lower than that of untreated, infected nude mice. The higher dose of IL-3 treatment from Day 4 to Day 13 (total 5.8 X 10(5) U) caused more profound reduction of LPG as early as Day 9, although complete cessation of LPG was not observed until Day 13, the end of this series of experiments. By this higher dose of IL-3 treatment, adult worms were completely expelled from the small intestine, although a small number of residual worms, which could explain the persistent low level of LPG detected from Day 9 to Day 13, was found in the caecum. Histological examination revealed that the number of MMC, especially in the epithelium, of the small intestine of IL-3-treated mice was significantly higher than that of untreated mice.

Abe T et al. (1992) J Helminthol "Protease resistant interleukin-3 stimulating components in excretory and secretory products from adult worms of Strongyloides ratti."

Yoshimura K, Abe T, Nawa Y

[J Helminthol, 1992]

Excretory and secretory (ES) products collected from adult worms of Strongyloides ratti stimulated interleukin-3 (IL-3) production with mesenteric lymph node cells from infected C57BL/6 mice, but not with normal mesenteric lymph node cells. The IL-3 stimulating components were not major IgG binding antigens. Activity of the IL-3 stimulating components was stable by treatment with protease, although reduced by heating in boiling water.

Abe T et al. (1993) J Helminthol "Strongyloides ratti: dissociation of immunological memory of the protection against tissue migrating larvae and intestinal adult worms in mice."

Nawa Y, Yoshimura K, Abe T

[J Helminthol, 1993]

Immunological memory generated by infection with S. ratti was studied separately in the migratory and intestinal phases in mice. Protection against reinfection in the migratory phase was 96-98% at 2 weeks but significantly decreased to 60% at 12 weeks after the primary infection. However, protection in the intestinal phase was 96% even 12 weeks after the primary infection. Recall of immunity against the intestinal phase persists for longer than that against the migratory phase in mice.

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.

Abe T et al. (1993) Parasite Immunol "Different susceptibility to the IL-3 induced-protective effects between Strongyloides ratti and Nippostrongylus brasiliensis in C57BL/6 mice."

Sugaya H, Yoshimura K, Abe T

[Parasite Immunol, 1993]

Repetitive administration of recombinant IL-3 induced protection against Strongyloides ratti but not against Nippostrongylus brasiliensis in C57BL/6 mice. Numbers of S. ratti were negligible from day 4 to day 6 post-infection in mice injected with IL-3, whereas N. brasiliensis burdens were almost equal from day 4 to day 6 between mice injected with IL-3 or with medium. Mice treated with IL-3 and then concurrently infected with S. ratti and N. brasiliensis were protected from intestinal S. ratti but not from N. brasiliensis. The numbers of intestinal mucosal mast cells were increased by the repetitive IL-3 treatment on one day after the final injection and was augmented by subsequent infection with both nematodes.

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.

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.

Samuel ADT et al. (2003) J Neurosci "Synaptic activity of the AFD neuron in Caenorhabditis elegans correlates with thermotactic memory."

Murthy VN, Samuel ADT, Silva RA

[J Neurosci, 2003]

Thermotactic behavior in Caenorhabditis elegans is sensitive to both a worm's ambient temperature (T-amb) and its memory of the temperature of its cultivation (T-cult). The AFD neuron is part of a neural circuit that underlies thermotactic behavior. By monitoring the fluorescence of pH-sensitive green fluorescent protein localized to synaptic vesicles, we measured the rate of the synaptic release of AFD in worms cultivated at temperatures between 15 and 25degreesC, and subjected to fixed, ambient temperatures in the same range. We found that the rate of AFD synaptic release is high if either T-amb > T-cult or T-amb > T-cult, but AFD synaptic release is low if T-amb congruent to T-cult. This suggests that AFD encodes a direct comparison between T-amb and T-cult.