CoChat
Sign Up
Cited by 249

The DOI matches its Crossref record.

Delayed Expulsion of the Nematode Trichinella spiralis In Mice Lacking the Mucosal Mast Cell–Specific Granule Chymase, Mouse Mast Cell Protease-1

Knight, Pamela A., Wright, Steven H., Lawrence, Catherine E., Paterson, Yvonne Y.W., Miller, Hugh R.P.·2000·The Journal of Experimental Medicine
DOI 10.1084/jem.192.12.1849PMC PMC2213497
Open this paper in CoChat — free account

Abstract

Expulsion of gastrointestinal nematodes is associated with pronounced mucosal mast cell (MMC) hyperplasia, differentiation, and activation, accompanied by the systemic release of MMC granule chymases (chymotrypsin-like serine proteases). The β-chymase mouse mast cell protease-1 (mMCP-1) is expressed predominantly by intraepithelial MMCs, and levels in the bloodstream and intestinal lumen are maximal at the time of worm expulsion in parasitized mice. To address the in vivo functions of MMC-specific β-chymases, we have generated transgenic mice that lack the mMCP-1 gene. They were backcrossed onto a congenic BALB/c background to investigate the response to nematode infection. The deletion of the mMCP-1 gene is associated with significantly delayed expulsion of Trichinella spiralis and increased deposition of muscle larvae in BALB/c mice despite the presence of normal and sometimes increased numbers of MMCs. Neither worm fecundity nor worm burdens were altered in Nippostrongylus-infected mMCP-1−/− BALB/c mice. These data demonstrate, for the first time, that the ablation of an MMC-derived effector molecule compromises the expulsion process.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1084/jem.192.12.1849

Cites

Statistics

Figures

Figure 1 (A) Mean total worm burdens (log10 [x + 1] + SE) from T. spiralis–infected mMCP-1+/+ (filled bars) and mMCP-1 −/− (open bars) BALB/c F7 mice. Representative of two experiments. (B) Mean total worm burdens (log10 [x + 1] + SE) and muscle larvae (day 30) (log10 [x + 1] + SE) from T. spiralis–infected mMCP-1+/+ and mMCP-1−/− BALB/c F10 mice. (C and E) Mast cell counts (+SE) in the jejunum from mMCP-1+/+ and mMCP-1−/− BALB/c F7 mice are shown 6, 14, and 18 d after primary infection with 500 T. spiralis muscle larvae per mouse (shown in A). The cells are counted per vcu in the epithelium and lamina propria (B; MMC/vcu) and in the submucosa (C; SMMC/vcu) underlying each vcu. (D and F) Mast cell counts (+SE) in the jejunum from mMCP-1+/+ and mMCP-1−/− BALB/c F10 mice 0–30 d after primary infection with 300 T. spiralis muscle larvae per mouse (shown in D).
Figure 1 (A) Mean total worm burdens (log10 [x + 1] + SE) from T. spiralis–infected mMCP-1+/+ (filled bars) and mMCP-1 −/− (open bars) BALB/c F7 mice. Representative of two experiments. (B) Mean total worm burdens (log10 [x + 1] + SE) and muscle larvae (day 30) (log10 [x + 1] + SE) from T. spiralis–infected mMCP-1+/+ and mMCP-1−/− BALB/c F10 mice. (C and E) Mast cell counts (+SE) in the jejunum from mMCP-1+/+ and mMCP-1−/− BALB/c F7 mice are shown 6, 14, and 18 d after primary infection with 500 T. spiralis muscle larvae per mouse (shown in A). The cells are counted per vcu in the epithelium and lamina propria (B; MMC/vcu) and in the submucosa (C; SMMC/vcu) underlying each vcu. (D and F) Mast cell counts (+SE) in the jejunum from mMCP-1+/+ and mMCP-1−/− BALB/c F10 mice 0–30 d after primary infection with 300 T. spiralis muscle larvae per mouse (shown in D).CC BY-NC-SA · PubMed Central
Figure 2 (A) Mean worm burdens (log10 [x + 1] + SE) in mMCP-1+/+ and mMCP-1−/− BALB/c F10 mice after primary infection on day 0 (1°) and challenge infection on day 21 (2°) with 300 T. spiralis muscle larvae per mouse. Data are shown 6 d after an initial primary infection (day 6 [1°]), 6 d after receiving the challenge dose (day 6 [2°]), and from an equivalent naive group that received the challenge dose only (day 6 [2° Con]). (B). Mast cell counts (+SE) in the jejunum from mMCP-1+/+ (WTs) and mMCP-1−/− (KOs) BALB/c F10 mice are shown 6 d after challenge infection with T. spiralis (shown in A). See legend for Fig. 1c and Fig. e. (C and D) Toluidine blue/eosin-stained jejunum from mMCP-1+/+ (C) and mMCP-1−/− (D) BALB/c F10 mice 6 d after challenge with T. spiralis. The reduced intensity of staining of MMCs in the villi in mMCP-1−/− jejunum is in accordance with previous data 11. Note the abundant mast cells in the submucosa of the mMCP-1−/− jejunum compared with that of mMCP-1+/+ jejunum.
Figure 2 (A) Mean worm burdens (log10 [x + 1] + SE) in mMCP-1+/+ and mMCP-1−/− BALB/c F10 mice after primary infection on day 0 (1°) and challenge infection on day 21 (2°) with 300 T. spiralis muscle larvae per mouse. Data are shown 6 d after an initial primary infection (day 6 [1°]), 6 d after receiving the challenge dose (day 6 [2°]), and from an equivalent naive group that received the challenge dose only (day 6 [2° Con]). (B). Mast cell counts (+SE) in the jejunum from mMCP-1+/+ (WTs) and mMCP-1−/− (KOs) BALB/c F10 mice are shown 6 d after challenge infection with T. spiralis (shown in A). See legend for Fig. 1c and Fig. e. (C and D) Toluidine blue/eosin-stained jejunum from mMCP-1+/+ (C) and mMCP-1−/− (D) BALB/c F10 mice 6 d after challenge with T. spiralis. The reduced intensity of staining of MMCs in the villi in mMCP-1−/− jejunum is in accordance with previous data 11. Note the abundant mast cells in the submucosa of the mMCP-1−/− jejunum compared with that of mMCP-1+/+ jejunum.CC BY-NC-SA · PubMed Central
Figure 3 (A) Mean fecal egg counts (log10 [x + 1] + SE) from mMCP-1+/+ (WTs) and mMCP-1−/− (KOs) BALB/c F10 mice after receiving a primary infection on day 0 with 500 N. brasiliensis larvae and challenge infection by gavage with 200 adult worms on day 21. (B) Mast cell counts (+SE) in the jejunum from mMCP-1+/+ (WTs) and mMCP-1−/− (KOs) BALB/c F10 mice 3 d after challenge infection with adult N. brasiliensis. See legend for Fig. 1c and Fig. e.
Figure 3 (A) Mean fecal egg counts (log10 [x + 1] + SE) from mMCP-1+/+ (WTs) and mMCP-1−/− (KOs) BALB/c F10 mice after receiving a primary infection on day 0 with 500 N. brasiliensis larvae and challenge infection by gavage with 200 adult worms on day 21. (B) Mast cell counts (+SE) in the jejunum from mMCP-1+/+ (WTs) and mMCP-1−/− (KOs) BALB/c F10 mice 3 d after challenge infection with adult N. brasiliensis. See legend for Fig. 1c and Fig. e.CC BY-NC-SA · PubMed Central
Figure 4 (A and B) Concentrations of mMCP-1 in the jejunum (A) (microgram per gram wet weight) and serum (B) (microgram per milliliter) from mMCP-1+/+ and mMCP-1−/− mice 0–30 d after infection with T. spiralis (shown in Fig. 1 B) and 6 d after challenge (2nd) (Fig. 2 A), as assessed by mMCP-1–specific ELISA. Note that mMCP-1 was undetectable in the mMCP-1−/− mice. (C) Transcription of chymase genes mMCP-1, -2, and -5 and the housekeeping gene GAPDH in total jejunal RNA from T. spiralis infected mMCP-1+/+ and mMCP-1−/− BALB/c F10 mice. Total RNA was extracted from uninfected jejunum (Un) and from jejunum 6 d after primary (1st) and challenge (2nd) infection with T. spiralis. For each primer set, tracks are loaded with reverse transcription PCR products from PCR reactions stopped after 16, 20, 24, and 28 thermocycles, plus a negative control (equivalent quantities of non–reverse-transcribed RNA amplified for 28 thermocycles), respectively.
Figure 4 (A and B) Concentrations of mMCP-1 in the jejunum (A) (microgram per gram wet weight) and serum (B) (microgram per milliliter) from mMCP-1+/+ and mMCP-1−/− mice 0–30 d after infection with T. spiralis (shown in Fig. 1 B) and 6 d after challenge (2nd) (Fig. 2 A), as assessed by mMCP-1–specific ELISA. Note that mMCP-1 was undetectable in the mMCP-1−/− mice. (C) Transcription of chymase genes mMCP-1, -2, and -5 and the housekeeping gene GAPDH in total jejunal RNA from T. spiralis infected mMCP-1+/+ and mMCP-1−/− BALB/c F10 mice. Total RNA was extracted from uninfected jejunum (Un) and from jejunum 6 d after primary (1st) and challenge (2nd) infection with T. spiralis. For each primer set, tracks are loaded with reverse transcription PCR products from PCR reactions stopped after 16, 20, 24, and 28 thermocycles, plus a negative control (equivalent quantities of non–reverse-transcribed RNA amplified for 28 thermocycles), respectively.CC BY-NC-SA · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 24

  1. Enerback, 1987, Mucosal mast cells in the rat and man, Int. Arch. Allergy Appl. Immunol., 82, 249, 10.1159/000234199 · DOI
  2. Befus, 1982, Mucosal mast cells 1. Isolation and functional characteristics of rat intestinal mast cells, J. Immunol., 128, 2475, 10.4049/jimmunol.128.6.2475 · DOI
  3. Miller, 1988, Granule proteases define mast cell heterogeneity in the serosa and gastrointestinal mucosa of the mouse, Immunology., 65, 559
  4. Stevens, 1994, Strain-specific and tissue specific expression of mouse mast cell secretory granule proteases, Proc. Natl. Acad. Sci. USA., 91, 128, 10.1073/pnas.91.1.128 · DOI
  5. Woodbury, 1984, Mucosal mast cells are functionally active during spontaneous expulsion of intestinal nematode infections in the rat, Nature., 312, 450, 10.1038/312450a0 · DOI
  6. Miller, 1996, Mucosal mast cells and the allergic response against nematode parasites, Vet. Immunol. Immunopathol., 54, 331, 10.1016/S0165-2427(96)05696-6 · DOI
  7. Scudamore, 1995, The release of the mucosal mast cell chymase, rat mast cell protease II, during anaphylaxis is associated with the rapid development of paracellular permeability to macromolecules in rat jejunum, J. Exp. Med, 182, 1871, 10.1084/jem.182.6.1871 · DOI
  8. Scudamore, 1998, The rat mucosal mast cell chymase, RMCP-II, alters epithelial cell monolayer permeability in association with altered distribution of the tight junction proteins ZO-1 and occludin, Eur. J. Cell. Biol, 75, 321, 10.1016/S0171-9335(98)80065-4 · DOI · Paper page
  9. Scudamore, 1997, Mast cell heterogeneity in the gastrointestinal tract. Variable expression of mouse mast cell protease-1 (mMCP-1) in intraepithelial mucosal mast cells in nematode-infected and normal BALB/c mice, Am. J. Pathol., 150, 1661
  10. Huntley, 1990, Distribution of intestinal mast cell protease in blood and tissues of normal and Trichinella-infected mice, Parasite Immunol., 12, 85, 10.1111/j.1365-3024.1990.tb00938.x · DOI
  11. Wastling, 1998, Histochemical and ultrastructural modification of mucosal mast cell granules in parasitized mice lacking the β-chymase, mouse mast cell protease-1, Am. J. Pathol., 153, 491, 10.1016/S0002-9440(10)65592-7 · DOI
  12. Urban, 1998, Il-13, IL-4Ra, and Stat6 are required for the expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis, Immunity., 8, 255, 10.1016/S1074-7613(00)80477-X · DOI
  13. Ha, 1983, Delayed expulsion of adult Trichinella spiralis by mast cell deficient W/Wv mice, Infect. Immun., 41, 445, 10.1128/iai.41.1.445-447.1983 · DOI
  14. Faulkner, 1997, Interleukin-9 is involved in host protective immunity to intestinal nematode infection, Eur. J. Immunol., 27, 2536, 10.1002/eji.1830271011 · DOI
  15. Wakelin, 1977, Transfer of immunity to Trichinella spiralis in the mouse with mesenteric lymph node cells in donors and expression of immunity in recipients, Parasitology., 74, 215, 10.1017/S0031182000047843 · DOI
  16. Miller, 1971, Immune reactions in mucous membranes. 1. Intestinal mast cell responses during helmith expulsion in the rat, Immunology., 20, 227
  17. Wastling, 1997, Constitutive expression of mouse mast cell protease-1 in normal BALB/c mice and its up-regulation during intestinal nematode infection, Immunology., 90, 308, 10.1046/j.1365-2567.1997.00155.x · DOI
  18. Lawrence, 1998, IL-4 regulated enteropathy in an intestinal nematode infection, Eur. J. Immunol., 28, 2672, 10.1002/(SICI)1521-4141(199809)28:09<2672::AID-IMMU2672>3.0.CO;2-F · DOI
  19. Donaldson, 1996, A critical role for stem cell factor and c-kit in host protective immunity to an intestinal helminth, Int. Immunol., 8, 559, 10.1093/intimm/8.4.559 · DOI
  20. Mitchell, 1983, Kinetics of expulsion of the nematode, Nippostrongylus brasiliensis, in mast-cell deficient W/Wv mice, Parasite Immunol., 4, 1, 10.1111/j.1365-3024.1983.tb00718.x · DOI
  21. Nawa, 1994, Selective effector mechanisms for the expulsion of intestinal helminths, Parasite Immunol., 16, 333, 10.1111/j.1365-3024.1994.tb00358.x · DOI
  22. Gurish, 1993, A closely linked complex of mouse mast cell-specific chymase genes on chromosome 14, J. Biol. Chem, 268, 11372, 10.1016/S0021-9258(18)82134-2 · DOI
  23. Friend, 1996, Mast cells that reside at different locations in the jejunum of mice infected with Trichinella spiralis exhibit sequential changes in their granule ultrastructure and chymase phenotype, J. Cell Biol, 135, 279, 10.1083/jcb.135.1.279 · DOI
  24. Friend, 2000, Senescent jejunal mast cells and eosinophils in the mouse translocate to the spleen and draining lymph node, respectively, during the recovery phase of helminth infection, J. Immunol., 165, 344, 10.4049/jimmunol.165.1.344 · DOI

Cited by

Sorted by citations

Metadata

Authors
Knight, P. A., Wright, S. H., Lawrence, C. E., Paterson, Y. Y. W., & Miller, H. R. P.
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2000-12-18
Volume
192
Issue
12
Pages
1849-1856
ISSN
  • 0022-1007
  • 1540-9538
DOI
10.1084/jem.192.12.1849
PMC
PMC2213497
Cited by
249
References
0
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review