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Bronchiolitis obliterans syndrome is associated with increased peripheral blood natural killer and natural killer T-like granzymes, perforin, and T-helper-type 1 pro-inflammatory cytokines.
J Heart Lung Transplant. 2012 Aug; 31(8):888-95.JH

Abstract

BACKGROUND

We previously showed that bronchiolitis obliterans syndrome (BOS) is associated with lack of immunosuppression of T-cell pro-inflammatory cytokines and granzyme B. We recently showed that natural killer (NK) T (NKT)-like cells are a major source of pro-inflammatory cytokines and granzymes in the blood of stable lung transplant patients. NK cells also produce these pro-inflammatory mediators, and we hypothesized that BOS may be associated with lack of immunosuppression of these pro-inflammatory mediators in NK and NKT-like cells.

METHOD

Granzyme, perforin, and intracellular cytokine profiles from stable transplant recipients, patients with evidence of BOS, and healthy controls were determined using multiparameter flow cytometry.

RESULTS

The percentage of NK cells expressing granzymes and perforin was significantly increased in BOS patients compared with stable patients and in stable patients compared with controls (89% ± 13%, 69% ± 12%, 33% ± 14% for NK and 35% ± 19%, 12% ± 15%, and 2% ± 3% for NKT-like granzyme B producing cells for BOS, stable patients and controls, respectively). There was an increase in the percentage of NK and NKT-like cells producing interferon (IFN)-γ and tumor necrosis factor (TNF)-α in BOS compared with stable patients (36% ± 16% and 10% ± 4% for NK and 32% ± 13% and 17% ± 8% for NKT-like IFN-γ producing cells for BOS and stable patients, respectively). There was a significant correlation between increased NK IFN-γ and TNF-α and values of forced expiratory volume in 1 second.

CONCLUSIONS

BOS is associated with increased peripheral blood NK and NKT-like cells expressing granzymes, perforin, and Th1 pro-inflammatory cytokines. These cells may migrate to the lungs and have an impact in airway damage in BOS. Therapeutic targeting of these pro-inflammatory mediators and monitoring response longitudinally using this assay may reduce BOS.

Authors+Show Affiliations

Lung Research, Hanson Institute, Royal Adelaide Hospital, Adelaide, SA 5006, Australia. greg.hodge@health.sa.gov.auNo 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

22759800

Citation

Hodge, Greg, et al. "Bronchiolitis Obliterans Syndrome Is Associated With Increased Peripheral Blood Natural Killer and Natural Killer T-like Granzymes, Perforin, and T-helper-type 1 Pro-inflammatory Cytokines." The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, vol. 31, no. 8, 2012, pp. 888-95.
Hodge G, Hodge S, Holmes-Liew CL, et al. Bronchiolitis obliterans syndrome is associated with increased peripheral blood natural killer and natural killer T-like granzymes, perforin, and T-helper-type 1 pro-inflammatory cytokines. J Heart Lung Transplant. 2012;31(8):888-95.
Hodge, G., Hodge, S., Holmes-Liew, C. L., Reynolds, P. N., & Holmes, M. (2012). Bronchiolitis obliterans syndrome is associated with increased peripheral blood natural killer and natural killer T-like granzymes, perforin, and T-helper-type 1 pro-inflammatory cytokines. The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, 31(8), 888-95. https://doi.org/10.1016/j.healun.2012.04.007
Hodge G, et al. Bronchiolitis Obliterans Syndrome Is Associated With Increased Peripheral Blood Natural Killer and Natural Killer T-like Granzymes, Perforin, and T-helper-type 1 Pro-inflammatory Cytokines. J Heart Lung Transplant. 2012;31(8):888-95. PubMed PMID: 22759800.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bronchiolitis obliterans syndrome is associated with increased peripheral blood natural killer and natural killer T-like granzymes, perforin, and T-helper-type 1 pro-inflammatory cytokines. AU - Hodge,Greg, AU - Hodge,Sandra, AU - Holmes-Liew,Chien-Li, AU - Reynolds,Paul N, AU - Holmes,Mark, PY - 2012/01/10/received PY - 2012/03/27/revised PY - 2012/04/29/accepted PY - 2012/7/5/entrez PY - 2012/7/5/pubmed PY - 2012/12/10/medline SP - 888 EP - 95 JF - The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation JO - J. Heart Lung Transplant. VL - 31 IS - 8 N2 - BACKGROUND: We previously showed that bronchiolitis obliterans syndrome (BOS) is associated with lack of immunosuppression of T-cell pro-inflammatory cytokines and granzyme B. We recently showed that natural killer (NK) T (NKT)-like cells are a major source of pro-inflammatory cytokines and granzymes in the blood of stable lung transplant patients. NK cells also produce these pro-inflammatory mediators, and we hypothesized that BOS may be associated with lack of immunosuppression of these pro-inflammatory mediators in NK and NKT-like cells. METHOD: Granzyme, perforin, and intracellular cytokine profiles from stable transplant recipients, patients with evidence of BOS, and healthy controls were determined using multiparameter flow cytometry. RESULTS: The percentage of NK cells expressing granzymes and perforin was significantly increased in BOS patients compared with stable patients and in stable patients compared with controls (89% ± 13%, 69% ± 12%, 33% ± 14% for NK and 35% ± 19%, 12% ± 15%, and 2% ± 3% for NKT-like granzyme B producing cells for BOS, stable patients and controls, respectively). There was an increase in the percentage of NK and NKT-like cells producing interferon (IFN)-γ and tumor necrosis factor (TNF)-α in BOS compared with stable patients (36% ± 16% and 10% ± 4% for NK and 32% ± 13% and 17% ± 8% for NKT-like IFN-γ producing cells for BOS and stable patients, respectively). There was a significant correlation between increased NK IFN-γ and TNF-α and values of forced expiratory volume in 1 second. CONCLUSIONS: BOS is associated with increased peripheral blood NK and NKT-like cells expressing granzymes, perforin, and Th1 pro-inflammatory cytokines. These cells may migrate to the lungs and have an impact in airway damage in BOS. Therapeutic targeting of these pro-inflammatory mediators and monitoring response longitudinally using this assay may reduce BOS. SN - 1557-3117 UR - https://www.unboundmedicine.com/medline/citation/22759800/Bronchiolitis_obliterans_syndrome_is_associated_with_increased_peripheral_blood_natural_killer_and_natural_killer_T_like_granzymes_perforin_and_T_helper_type_1_pro_inflammatory_cytokines_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1053-2498(12)01078-9 DB - PRIME DP - Unbound Medicine ER -