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Inducible nitric oxide synthase expression in the intestinal muscularis mediates severe smooth muscle dysfunction during acute rejection in allogenic rodent small bowel transplantation.
J Surg Res 2008; 150(2):159-68JS

Abstract

BACKGROUND

Acute rejection in small bowel transplantation is associated with dysmotility. Therefore, host and organ not only face the threat of destructive immunological processes but also the risk of bacterial translocation, endotoxemia, and systemic inflammatory response syndrome. We hypothesized that dysmotility during acute rejection is based on an alloreactive leukocyte infiltrate and coexpression of the kinetically active mediator inducible nitric oxide synthase (iNOS) in the muscularis propria.

MATERIALS AND METHODS

Allogenic and isogenic rat small bowel transplantation (SBTx; Brown Norway [BN] to Lewis and BN to BN) was performed without immunosuppression. Animals were sacrificed 4 and 7 d after SBTx. Leukocyte infiltration and iNOS protein was investigated by immunohistochemistry and immunohistology. Real-time reverse transcription polymer chain reaction was used to detect iNOS expression. Griess reaction was used to evaluate NO production. Spontaneous, bethanechol-stimulated, and L-N(6)-(1-iminoethyl)-L-Lysin-blocked jejunal circular muscle contractions were measured in a standard organ bath in vitro.

RESULTS

On d 7 after SBTx, allogenic transplanted animals showed significant infiltration with ED-1- and ED-2-positive monocytes and macrophages within the muscularis parallel to the manifestation of acute rejection. Additionally, immunohistochemistry localized iNOS protein in leukocytes within the muscularis. Reverse transcription polymer chain reaction showed a significant increase in iNOS mRNA expression (460-fold) in allogenic transplanted muscularis compared to isogenic transplanted muscularis (2.5-fold). Compared to controls, allogenic grafts showed a 73% decrease in smooth muscle contractility, while isogenic grafts showed only an 8% decrease of contractility on d 7. L-N(6)-(1-iminoethyl)-L-Lysin application in vitro significantly improved muscle contractility and decreased NO production.

CONCLUSION

The data show that inflammation associated iNOS expression in the intestinal graft muscularis is involved in motoric graft dysfunction during acute rejection.

Authors+Show Affiliations

Department of Surgery, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany. nico.schaefer@ukb.uni-bonn.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18805549

Citation

Schaefer, Nico, et al. "Inducible Nitric Oxide Synthase Expression in the Intestinal Muscularis Mediates Severe Smooth Muscle Dysfunction During Acute Rejection in Allogenic Rodent Small Bowel Transplantation." The Journal of Surgical Research, vol. 150, no. 2, 2008, pp. 159-68.
Schaefer N, Tahara K, Pech T, et al. Inducible nitric oxide synthase expression in the intestinal muscularis mediates severe smooth muscle dysfunction during acute rejection in allogenic rodent small bowel transplantation. J Surg Res. 2008;150(2):159-68.
Schaefer, N., Tahara, K., Pech, T., Websky, M. V., Fujishiro, J., Pantelis, D., ... Türler, A. (2008). Inducible nitric oxide synthase expression in the intestinal muscularis mediates severe smooth muscle dysfunction during acute rejection in allogenic rodent small bowel transplantation. The Journal of Surgical Research, 150(2), pp. 159-68. doi:10.1016/j.jss.2008.01.019.
Schaefer N, et al. Inducible Nitric Oxide Synthase Expression in the Intestinal Muscularis Mediates Severe Smooth Muscle Dysfunction During Acute Rejection in Allogenic Rodent Small Bowel Transplantation. J Surg Res. 2008;150(2):159-68. PubMed PMID: 18805549.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inducible nitric oxide synthase expression in the intestinal muscularis mediates severe smooth muscle dysfunction during acute rejection in allogenic rodent small bowel transplantation. AU - Schaefer,Nico, AU - Tahara,Kazunori, AU - Pech,Thomas, AU - Websky,Martin V, AU - Fujishiro,Jun, AU - Pantelis,Dimitrios, AU - Abu-Elmagd,Kareem, AU - Kalff,Jörg C, AU - Hirner,Andreas, AU - Türler,Andreas, Y1 - 2008/02/29/ PY - 2007/06/25/received PY - 2007/12/10/revised PY - 2008/01/10/accepted PY - 2008/9/23/pubmed PY - 2009/1/24/medline PY - 2008/9/23/entrez SP - 159 EP - 68 JF - The Journal of surgical research JO - J. Surg. Res. VL - 150 IS - 2 N2 - BACKGROUND: Acute rejection in small bowel transplantation is associated with dysmotility. Therefore, host and organ not only face the threat of destructive immunological processes but also the risk of bacterial translocation, endotoxemia, and systemic inflammatory response syndrome. We hypothesized that dysmotility during acute rejection is based on an alloreactive leukocyte infiltrate and coexpression of the kinetically active mediator inducible nitric oxide synthase (iNOS) in the muscularis propria. MATERIALS AND METHODS: Allogenic and isogenic rat small bowel transplantation (SBTx; Brown Norway [BN] to Lewis and BN to BN) was performed without immunosuppression. Animals were sacrificed 4 and 7 d after SBTx. Leukocyte infiltration and iNOS protein was investigated by immunohistochemistry and immunohistology. Real-time reverse transcription polymer chain reaction was used to detect iNOS expression. Griess reaction was used to evaluate NO production. Spontaneous, bethanechol-stimulated, and L-N(6)-(1-iminoethyl)-L-Lysin-blocked jejunal circular muscle contractions were measured in a standard organ bath in vitro. RESULTS: On d 7 after SBTx, allogenic transplanted animals showed significant infiltration with ED-1- and ED-2-positive monocytes and macrophages within the muscularis parallel to the manifestation of acute rejection. Additionally, immunohistochemistry localized iNOS protein in leukocytes within the muscularis. Reverse transcription polymer chain reaction showed a significant increase in iNOS mRNA expression (460-fold) in allogenic transplanted muscularis compared to isogenic transplanted muscularis (2.5-fold). Compared to controls, allogenic grafts showed a 73% decrease in smooth muscle contractility, while isogenic grafts showed only an 8% decrease of contractility on d 7. L-N(6)-(1-iminoethyl)-L-Lysin application in vitro significantly improved muscle contractility and decreased NO production. CONCLUSION: The data show that inflammation associated iNOS expression in the intestinal graft muscularis is involved in motoric graft dysfunction during acute rejection. SN - 1095-8673 UR - https://www.unboundmedicine.com/medline/citation/18805549/Inducible_nitric_oxide_synthase_expression_in_the_intestinal_muscularis_mediates_severe_smooth_muscle_dysfunction_during_acute_rejection_in_allogenic_rodent_small_bowel_transplantation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-4804(08)00043-7 DB - PRIME DP - Unbound Medicine ER -