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Article ; Online: Selective CD117

Manz, Markus G / Russkamp, Norman F

2019 Volume 133, Issue 19, Page(s) 2007–2009

MeSH term(s)	Animals ; Hematopoietic Stem Cells ; Heterografts ; Humans ; Mice ; Myelodysplastic Syndromes ; Proto-Oncogene Proteins c-kit
Chemical Substances	Proto-Oncogene Proteins c-kit (EC 2.7.10.1)
Language	English
Publishing date	2019-05-08
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2019-03-900894
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Zs.MO 364: Show issues

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Article ; Online: Anti-CD117 immunotherapy to eliminate hematopoietic and leukemia stem cells.

Russkamp, Norman F / Myburgh, Renier / Kiefer, Jonathan D / Neri, Dario / Manz, Markus G

Experimental hematology

2021 Volume 95, Page(s) 31–45

Abstract: Precise replacement of diseased or dysfunctional organs is the goal of regenerative medicine and has appeared to be a distant goal for a long time. In the field of hematopoietic stem cell transplantation, this goal is now becoming tangible as gene- ... ...

Abstract	Precise replacement of diseased or dysfunctional organs is the goal of regenerative medicine and has appeared to be a distant goal for a long time. In the field of hematopoietic stem cell transplantation, this goal is now becoming tangible as gene-editing technologies and novel conditioning agents are entering the clinical arena. Targeted immunologic depletion of hematopoietic stem cells (HSCs), which are at the very root of the hematopoietic system, will enable more selective and potentially more effective hematopoietic stem cell transplantation in patients with hematological diseases. In contrast to current conditioning regimes based on ionizing radiation and chemotherapy, immunologic conditioning will spare mature hematopoietic cells and cause substantially less inflammation and unspecific collateral damage to other organs. Biological agents that target the stem cell antigen CD117 are the frontrunners for this purpose and have exhibited preclinical activity in depletion of healthy HSCs. The value of anti-CD117 antibodies as conditioning agents is currently being evaluated in early clinical trials. Whereas mild, antibody-based immunologic conditioning concepts might be appropriate for benign hematological disorders in which incomplete replacement of diseased cells is sufficient, higher efficacy will be required for treatment and elimination of hematologic stem cell malignancies such as acute myeloid leukemia and myelodysplastic syndrome. Antibody-drug conjugates, bispecific T-cell engaging and activating antibodies (TEAs), or chimeric antigen receptor (CAR) T cells might offer increased efficacy compared with naked antibodies and yet higher tolerability and safety compared with current genotoxic conditioning approaches. Here, we summarize the current state regarding immunologic conditioning concepts for the treatment of HSC disorders and outline potential future developments.
MeSH term(s)	Animals ; Antibodies, Bispecific/therapeutic use ; Antineoplastic Agents/pharmacology ; Clinical Trial Protocols as Topic ; Clonal Hematopoiesis ; Combined Modality Therapy ; Genetic Diseases, Inborn/therapy ; Hematologic Neoplasms/therapy ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/drug effects ; Humans ; Immunoglobulin G/immunology ; Immunoglobulin G/therapeutic use ; Immunotherapy/methods ; Immunotherapy, Adoptive ; Immunotoxins/therapeutic use ; Leukemia, Myeloid, Acute/therapy ; Myelodysplastic Syndromes/therapy ; Neoplastic Stem Cells/drug effects ; Preleukemia/therapy ; Proto-Oncogene Proteins c-kit/antagonists & inhibitors ; Proto-Oncogene Proteins c-kit/biosynthesis ; Proto-Oncogene Proteins c-kit/genetics ; Proto-Oncogene Proteins c-kit/immunology ; Risk Assessment ; Severe Combined Immunodeficiency/therapy ; Transplantation Conditioning/methods
Chemical Substances	Antibodies, Bispecific ; Antineoplastic Agents ; Immunoglobulin G ; Immunotoxins ; KIT protein, human (EC 2.7.10.1) ; Proto-Oncogene Proteins c-kit (EC 2.7.10.1)
Language	English
Publishing date	2021-01-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	185107-x
ISSN	1873-2399 ; 0531-5573 ; 0301-472X
ISSN (online)	1873-2399
ISSN	0531-5573 ; 0301-472X
DOI	10.1016/j.exphem.2021.01.003
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Article ; Online: Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report.

Koch, Christian / Fleischer, Juliane / Popov, Todor / Frontzek, Karl / Schreiner, Bettina / Roth, Patrick / Manz, Markus G / Unseld, Simone / Müller, Antonia M S / Russkamp, Norman F

Journal for immunotherapy of cancer

2023 Volume 11, Issue 1

Abstract: Background: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common adverse event of CD19-directed chimeric antigen receptor (CAR) T cell therapy. Other neurological adverse events, however, have not methodically been described and ... ...

Abstract	Background: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common adverse event of CD19-directed chimeric antigen receptor (CAR) T cell therapy. Other neurological adverse events, however, have not methodically been described and studied. Furthermore, safety data on CAR-T cell therapy in patients with central nervous system (CNS) lymphoma remain limited. Main body: We here report occurrence of a Guillain-Barré-like syndrome (GBS) and central diabetes insipidus (cDI) following tisagenlecleucel therapy for relapsed high-grade lymphoma with CNS involvement. Both complications were refractory to standard treatment of ICANS. Weakness of respiratory muscles required mechanical ventilation and tracheostomy while cDI was treated with desmopressin substitution for several weeks. Muscle-nerve biopsy and nerve conduction studies confirmed an axonal pattern of nerve damage. T cell-rich infiltrates and detection of the CAR transgene in muscle-nerve sections imply a direct or indirect role of CAR-T cell-mediated inflammation. In line with current treatment guidelines for GBS, intravenous immunoglobulin was administered and gradual but incomplete recovery was observed over the course of several months. Conclusions: This case report highlights the risk of rare but severe neurological adverse events, such as acute GBS or cDI, in patients treated with CAR-T cells. It further underlines the importance of appropriate patient surveillance and systematic reporting of rare complications to eventually improve treatment.
MeSH term(s)	Humans ; Receptors, Chimeric Antigen ; Immunotherapy, Adoptive/adverse effects ; Lymphoma, Non-Hodgkin ; Central Nervous System Neoplasms ; Diabetes Insipidus/etiology ; Cell- and Tissue-Based Therapy ; Diabetes Mellitus
Chemical Substances	Receptors, Chimeric Antigen ; cell-associated neurotoxicity
Language	English
Publishing date	2023-01-23
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2022-006059
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Article ; Online: Disruption of CSF-1R signaling inhibits growth of AML with inv(16).

Simonis, Alexander / Russkamp, Norman F / Mueller, Jan / Wilk, C Matthias / Wildschut, Mattheus H E / Myburgh, Renier / Wildner-Verhey van Wijk, Nicole / Mueller, Rouven / Balabanov, Stefan / Valk, Peter J M / Theocharides, Alexandre P A / Manz, Markus G

Blood advances

2021 Volume 5, Issue 5, Page(s) 1273–1277

MeSH term(s)	Humans ; Leukemia, Myeloid, Acute ; Receptor Protein-Tyrosine Kinases ; Signal Transduction
Chemical Substances	Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2021-03-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2020003125
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Article ; Online: Fingerprinting of the TLR4-induced acute inflammatory response.

Bosmann, Markus / Russkamp, Norman F / Ward, Peter A

Experimental and molecular pathology

2012 Volume 93, Issue 3, Page(s) 319–323

Abstract: Intensive scientific efforts in the past decades have helped shed light into the pathogenesis of endotoxin-induced inflammation. We have used multiplexing bead-based assays to characterize the responses in two models of in vivo LPS challenge. C57BL/6 ... ...

Abstract	Intensive scientific efforts in the past decades have helped shed light into the pathogenesis of endotoxin-induced inflammation. We have used multiplexing bead-based assays to characterize the responses in two models of in vivo LPS challenge. C57BL/6 mice were either injected intraperitoneally (endotoxemia) or intratracheally (acute lung injury; ALI) with lipopolysaccharide (LPS). The time courses (1h-24h) of the following 20 inflammatory mediators in plasma or broncho-alveolar lavages were simultaneously analyzed: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-12(p40), IL-13, Eotaxin (CCL11), G-CSF, GM-CSF, IFN-γ, KC (CXCL1), MCP-1 (CCL2), MIP-1α (CCL3), MIP-1β (CCL4), RANTES (CCL5) and TNF-α. While significant inductions of all mediators were found, substantial differences in their absolute concentrations, time points of maximal concentrations and clearances were observed. There were also notable variations in the patterns of several cytokines/chemokines when samples from endotoxemia and LPS-ALI were compared. These data may be helpful in defining analytic strategies including selection of optimal time points for studying the host immune response to endotoxin.
MeSH term(s)	Acute Lung Injury/chemically induced ; Acute Lung Injury/immunology ; Animals ; Bronchoalveolar Lavage Fluid/chemistry ; Bronchoalveolar Lavage Fluid/cytology ; Bronchoalveolar Lavage Fluid/immunology ; Chemokines/analysis ; Chemokines/metabolism ; Endotoxemia/etiology ; Endotoxemia/immunology ; Escherichia coli/immunology ; Immunoassay/methods ; Injections, Intraperitoneal ; Intubation, Intratracheal ; Lipopolysaccharides/administration & dosage ; Male ; Mice ; Mice, Inbred C57BL ; Toll-Like Receptor 4/metabolism
Chemical Substances	Chemokines ; Lipopolysaccharides ; Tlr4 protein, mouse ; Toll-Like Receptor 4
Language	English
Publishing date	2012-09-06
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	207655-x
ISSN	1096-0945 ; 0014-4800
ISSN (online)	1096-0945
ISSN	0014-4800
DOI	10.1016/j.yexmp.2012.08.006
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Zs.A 183: Show issues

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Article: Fingerprinting of the TLR4-induced acute inflammatory response

Bosmann, Markus / Russkamp, Norman F / Ward, Peter A

Experimental and molecular pathology. 2012 Dec., v. 93, no. 3

2012

Abstract	Intensive scientific efforts in the past decades have helped shed light into the pathogenesis of endotoxin-induced inflammation. We have used multiplexing bead-based assays to characterize the responses in two models of in vivo LPS challenge. C57BL/6 mice were either injected intraperitoneally (endotoxemia) or intratracheally (acute lung injury; ALI) with lipopolysaccharide (LPS). The time courses (1h–24h) of the following 20 inflammatory mediators in plasma or broncho-alveolar lavages were simultaneously analyzed: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-12(p40), IL-13, Eotaxin (CCL11), G-CSF, GM-CSF, IFN-γ, KC (CXCL1), MCP-1 (CCL2), MIP-1α (CCL3), MIP-1β (CCL4), RANTES (CCL5) and TNF-α. While significant inductions of all mediators were found, substantial differences in their absolute concentrations, time points of maximal concentrations and clearances were observed. There were also notable variations in the patterns of several cytokines/chemokines when samples from endotoxemia and LPS-ALI were compared. These data may be helpful in defining analytic strategies including selection of optimal time points for studying the host immune response to endotoxin.
Keywords	chemokine CCL11 ; chemokine CCL2 ; chemokine CCL3 ; chemokine CCL4 ; chemokine CCL5 ; chemokine CXCL1 ; endotoxemia ; endotoxins ; granulocyte colony-stimulating factor ; granulocyte-macrophage colony-stimulating factor ; immune response ; inflammation ; interferon-gamma ; interleukin-12 ; interleukin-13 ; interleukin-1alpha ; interleukin-1beta ; interleukin-2 ; interleukin-3 ; interleukin-4 ; interleukin-5 ; interleukin-6 ; interleukin-9 ; lipopolysaccharides ; mice ; models ; pathogenesis ; tumor necrosis factor-alpha
Language	English
Dates of publication	2012-12
Size	p. 319-323.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	207655-x
ISSN	1096-0945 ; 0014-4800
ISSN (online)	1096-0945
ISSN	0014-4800
DOI	10.1016/j.yexmp.2012.08.006
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 183: Show issues

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Article ; Online: Experimental design of complement component 5a-induced acute lung injury (C5a-ALI): a role of CC-chemokine receptor type 5 during immune activation by anaphylatoxin.

Russkamp, Norman F / Ruemmler, Robert / Roewe, Julian / Moore, Bethany B / Ward, Peter A / Bosmann, Markus

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2015 Volume 29, Issue 9, Page(s) 3762–3772

Abstract: Excessive activation of the complement system is detrimental in acute inflammatory disorders. In this study, we analyzed the role of complement-derived anaphylatoxins in the pathogenesis of experimental acute lung injury/acute respiratory distress ... ...

Abstract	Excessive activation of the complement system is detrimental in acute inflammatory disorders. In this study, we analyzed the role of complement-derived anaphylatoxins in the pathogenesis of experimental acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in C57BL/6J mice. Intratracheal administration of recombinant mouse complement component (C5a) caused alveolar inflammation with abundant recruitment of Ly6-G(+)CD11b(+) leukocytes to the alveolar spaces and severe alveolar-capillary barrier dysfunction (C5a-ALI; EC(50[C5a]) = 20 ng/g body weight). Equimolar concentrations of C3a or desarginated C5a (C5a(desArg)) did not induce alveolar inflammation. The severity of C5a-ALI was aggravated in C5-deficient mice. Depletion of Ly6-G(+) cells and use of C5aR1(-/-) bone marrow chimeras suggested an essential role of C5aR1(+) hematopoietic cells in C5a-ALI. Blockade of PI3K/Akt and MEK1/2 kinase pathways completely abrogated lung injury. The mechanistic description is that C5a altered the alveolar cytokine milieu and caused significant release of CC-chemokines. Mice with genetic deficiency of CC-chemokine receptor (CCR) type 5, the common receptor of chemokine (C-C motif) ligand (CCL) 3, CCL4, and CCL5, displayed reduced lung damage. Moreover, treatment with a CCR5 antagonist, maraviroc, was protective against C5a-ALI. In summary, our results suggest that the detrimental effects of C5a in this model are partly mediated through CCR5 activation downstream of C5aR1, which may be evaluated for potential therapeutic exploitation in ALI/ARDS.
MeSH term(s)	Acute Lung Injury/drug therapy ; Acute Lung Injury/genetics ; Acute Lung Injury/metabolism ; Acute Lung Injury/pathology ; Animals ; CCR5 Receptor Antagonists/pharmacology ; Complement Activation ; Complement C3a/genetics ; Complement C3a/metabolism ; Complement C5a, des-Arginine/genetics ; Complement C5a, des-Arginine/metabolism ; Cyclohexanes/pharmacology ; Leukocytes/metabolism ; Leukocytes/pathology ; MAP Kinase Kinase 1/genetics ; MAP Kinase Kinase 1/metabolism ; MAP Kinase Kinase 2/genetics ; MAP Kinase Kinase 2/metabolism ; Mice ; Mice, Knockout ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Pulmonary Alveoli/metabolism ; Pulmonary Alveoli/pathology ; Receptor, Anaphylatoxin C5a/genetics ; Receptor, Anaphylatoxin C5a/metabolism ; Receptors, CCR5/genetics ; Receptors, CCR5/metabolism ; Triazoles/pharmacology
Chemical Substances	C5ar1 protein, mouse ; CCR5 Receptor Antagonists ; CCR5 protein, mouse ; Complement C5a, des-Arginine ; Cyclohexanes ; Receptor, Anaphylatoxin C5a ; Receptors, CCR5 ; Triazoles ; Complement C3a (80295-42-7) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; MAP Kinase Kinase 1 (EC 2.7.12.2) ; MAP Kinase Kinase 2 (EC 2.7.12.2) ; Map2k1 protein, mouse (EC 2.7.12.2) ; Map2k2 protein, mouse (EC 2.7.12.2) ; maraviroc (MD6P741W8A)
Language	English
Publishing date	2015-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.15-271635
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Zs.A 2266: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 296: Show issues

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Article ; Online: Long-Term Follow-Up of Antibody Titers Against Measles, Mumps, and Rubella in Recipients of Allogenic Hematopoietic Cell Transplantation.

Bögeholz, Jan / Russkamp, Norman F / Wilk, Christian M / Gourri, Elise / Haralambieva, Eugenia / Schanz, Urs / Mueller, Nicolas J / Manz, Markus G / Müller, Antonia M S

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

2019 Volume 26, Issue 3, Page(s) 581–592

Abstract: Outbreaks of viral infections, such as measles, are regularly observed and pose a serious threat to recipients of allogeneic hematopoietic cell transplantation (HCT). The questions of how long cellular and humoral protective host immunity persists, and ... ...

Abstract	Outbreaks of viral infections, such as measles, are regularly observed and pose a serious threat to recipients of allogeneic hematopoietic cell transplantation (HCT). The questions of how long cellular and humoral protective host immunity persists, and whether donor immunity can be transferred has not been clarified. Here we present a retrospective analysis of humoral immunity-serial antibody titers against measles, mumps, and rubella-in 331 patients who underwent allogeneic HCT at our single center between 2002 and 2015. Associations between the loss of protective antibody levels and clinical patient characteristics and transplantation parameters were examined. In general, antibody protection against measles persisted longer, with 72% of patients maintaining sufficient titers at 5 years post-HCT even without revaccination, while at that time only 65% and 50% of patients had protective immunity against rubella and mumps, respectively. The great majority of donors were seropositive for all 3 viruses; however, it appeared that donor humoral immunity could not be transferred and had no impact on post-HCT serostatus. Rather, the most relevant factor for persistent protective antibody titers against measles and rubella was whether patients were born before the introduction of the respective vaccine and thus were immunized by the wild-type disease-inducing virus instead of the vaccine. Moreover, the presence of moderate and severe chronic graft-versus-host disease (GVHD) was associated with more rapid loss of immune protection. In contrast, underlying disease, intensity of the conditioning regimen, use of antithymocyte globulin, age, and graft source had no influence on antibody titers. Overall, our findings suggest that the majority of antibodies against measles, mumps, and rubella originate from residual host cells, whereas donor immune status appears to have no influence on antibody protection post-HCT.
MeSH term(s)	Antibodies, Viral ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Humans ; Measles/prevention & control ; Measles-Mumps-Rubella Vaccine ; Mumps/prevention & control ; Retrospective Studies ; Rubella/prevention & control
Chemical Substances	Antibodies, Viral ; Measles-Mumps-Rubella Vaccine
Language	English
Publishing date	2019-11-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1474865-4
ISSN	1523-6536 ; 1083-8791
ISSN (online)	1523-6536
ISSN	1083-8791
DOI	10.1016/j.bbmt.2019.10.027
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Zs.A 5082: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 462: Show issues

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Article ; Online: Anti-human CD117 CAR T-cells efficiently eliminate healthy and malignant CD117-expressing hematopoietic cells.

Myburgh, Renier / Kiefer, Jonathan D / Russkamp, Norman F / Magnani, Chiara F / Nuñez, Nicolás / Simonis, Alexander / Pfister, Surema / Wilk, C Matthias / McHugh, Donal / Friemel, Juliane / Müller, Antonia M / Becher, Burkhard / Münz, Christian / van den Broek, Maries / Neri, Dario / Manz, Markus G

Leukemia

2020 Volume 34, Issue 10, Page(s) 2688–2703

Abstract: Acute myeloid leukemia (AML) initiating and sustaining cells maintain high cell-surface similarity with their cells-of-origin, i.e., hematopoietic stem and progenitor cells (HSPCs), and identification of truly distinguishing leukemia-private antigens has ...

Abstract	Acute myeloid leukemia (AML) initiating and sustaining cells maintain high cell-surface similarity with their cells-of-origin, i.e., hematopoietic stem and progenitor cells (HSPCs), and identification of truly distinguishing leukemia-private antigens has remained elusive to date. To nonetheless utilize surface antigen-directed immunotherapy in AML, we here propose targeting both, healthy and malignant human HSPC, by chimeric antigen receptor (CAR) T-cells with specificity against CD117, the cognate receptor for stem cell factor. This approach should spare most mature hematopoietic cells and would require CAR T termination followed by subsequent transplantation of healthy HSPCs to rescue hematopoiesis. We successfully generated anti-CD117 CAR T-cells from healthy donors and AML patients. Anti-CD117 CAR T-cells efficiently targeted healthy and leukemic CD117-positive cells in vitro. In mice xenografted with healthy human hematopoiesis, they eliminated CD117-expressing, but not CD117-negative human cells. Importantly, in mice xenografted with primary human CD117-positive AML, they eradicated disease in a therapeutic setting. Administration of ATG in combination with rituximab, which binds to the co-expressed CAR T-cell transduction/selection marker RQR8, led to CAR T-cell depletion. Thus, we here provide the first proof of concept for the generation and preclinical efficacy of CAR T-cells directed against CD117-expressing human hematopoietic cells.
MeSH term(s)	Animals ; Biomarkers ; Biopsy ; Bone Marrow/metabolism ; Bone Marrow/pathology ; Cell Line, Tumor ; Disease Models, Animal ; Gene Expression ; Hematologic Neoplasms/diagnosis ; Hematologic Neoplasms/immunology ; Hematologic Neoplasms/metabolism ; Hematologic Neoplasms/therapy ; Hematopoietic Stem Cells/immunology ; Hematopoietic Stem Cells/metabolism ; Humans ; Immunophenotyping ; Immunotherapy, Adoptive ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/immunology ; Leukemia, Myeloid, Acute/pathology ; Leukemia, Myeloid, Acute/therapy ; Lymphocyte Depletion ; Mice ; Proto-Oncogene Proteins c-kit/antagonists & inhibitors ; Proto-Oncogene Proteins c-kit/genetics ; Proto-Oncogene Proteins c-kit/metabolism ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; Receptors, Chimeric Antigen/genetics ; Receptors, Chimeric Antigen/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Treatment Outcome ; Xenograft Model Antitumor Assays
Chemical Substances	Biomarkers ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen ; KIT protein, human (EC 2.7.10.1) ; Proto-Oncogene Proteins c-kit (EC 2.7.10.1)
Language	English
Publishing date	2020-05-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-020-0818-9
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Zs.A 2295: Show issues

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Article ; Online: CD11c+ alveolar macrophages are a source of IL-23 during lipopolysaccharide-induced acute lung injury.

Bosmann, Markus / Grailer, Jamison J / Russkamp, Norman F / Ruemmler, Robert / Zetoune, Firas S / Sarma, J Vidya / Ward, Peter A

Shock (Augusta, Ga.)

2013 Volume 39, Issue 5, Page(s) 447–452

Abstract: Acute lung injury (ALI) is a severe pulmonary disease causing high numbers of fatalities worldwide. Innate immune responses are an integral part of the pathophysiologic events during ALI. Interleukin 23 (IL-23) is a proinflammatory mediator known to ... ...

Abstract	Acute lung injury (ALI) is a severe pulmonary disease causing high numbers of fatalities worldwide. Innate immune responses are an integral part of the pathophysiologic events during ALI. Interleukin 23 (IL-23) is a proinflammatory mediator known to direct the inflammatory responses in various settings of infection, autoimmunity, and cancer. Interleukin 23 has been associated with proliferation and effector functions in T(H)17 cells. Surprisingly, little is known about production of IL-23 during ALI. In this study, we found expression of mRNA for IL-23p19 to be 10-fold elevated in lung homogenates of C57BL/6 mice after lipopolysaccharide (LPS)-induced ALI. Likewise, concentrations of IL-23 significantly increased in bronchoalveolar lavage fluids. Experiments with IL-23-deficient mice showed that endogenous IL-23 was required for production of IL-17A during LPS-ALI. CD11c-diphtheria toxin receptor transgenic mice were used to selectively deplete CD11c cells, the data suggesting that IL-23 production is dependent at least in part on CD11c cells during ALI. No alterations of IL-23 levels were observed in Rag-1-deficient mice as compared with wild-type C57BL/6 mice following ALI. The mouse alveolar macrophage cell line, MH-S, as well as primary alveolar macrophages displayed abundant surface expression of CD11c. Activation of these macrophages by LPS resulted in release of IL-23 in vitro. Our findings identify CD11c macrophages in the lung are likely an important source of IL-23 during ALI, which may be helpful for better understanding of this disease.
MeSH term(s)	Acute Lung Injury/chemically induced ; Acute Lung Injury/immunology ; Animals ; CD11c Antigen/metabolism ; Interleukin-23/metabolism ; Lipopolysaccharides/toxicity ; Macrophages, Alveolar/metabolism ; Male ; Mice
Chemical Substances	CD11c Antigen ; Interleukin-23 ; Lipopolysaccharides
Language	English
Publishing date	2013-03-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1185432-7
ISSN	1540-0514 ; 1073-2322
ISSN (online)	1540-0514
ISSN	1073-2322
DOI	10.1097/SHK.0b013e31828f9c92
Database	MEDical Literature Analysis and Retrieval System OnLINE

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