Patrick G. Arndt, MD

Associate Professor of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine

Patrick G. Arndt

Contact Info

arndt108@umn.edu

Office Phone 612-626-4871

Mailing Address:
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine
420 Delaware Street, SE, MMC 276 (Pulmonary) MMC 434 (Allergy)
Minneapolis, MN 55455

Administrative Assistant Name
PACCS

Administrative Phone
612-624-0999

Administrative Email
paccmed@umn.edu

Administrative Fax Number
612-625-2174

Associate Professor of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine

Microbiology, Immunology and Cancer Biology (MICaB) Ph.D. Graduate Program


Pulmonologist and Critical Care Physician (also at Southdale MICU)


Medical School, University of Kentucky, Lexington

Residency, University of Colorado Health Sciences Center, Denver

Fellowship, University of Colorado Health Sciences Center, Denver

Summary

My research focuses on innate immunity and in particular the response of neutrophils to exogenous bacterial components or endogenous stress signals. Our main focus of disease is acute lung injury and the acute respiratory distress syndrome (ARDS) with our overall goal to improve patient outcomes in ARDS, a disease still associated with significant morbidity and mortality. Through examination of cell signaling pathways utilized by neutrophils in their response to stress mediators, we hope to identify targets that may be useful in dampening the response of neutrophils and accordingly decrease the severity of lung injury and the development of acute respiratory failure. Our major area of focus has been dissecting the pathways used by the mitogen activated protein kinase family of cell signaling molecules in order to better understand their upstream and downstream signaling components that induce and regulate the cellular activation of neutrophils. These identified components can then be assessed for their potential as modifiable targets for the treatment of ARDS at the bedside by drug or genetic approaches with the ultimate goal of improving patient outcomes.

Professional Associations

  • American Thoracic Society (ATS)
  • Chest

Research

Research Summary/Interests

Cell signaling, acute lung inflammation

The neutrophil is crucial to the inflammatory response and in particular to the pathophysiology of the acute respiratory distress syndrome (ARDS). Although neutrophil recruitment to sites of acute inflammation is beneficial, an over-exuberant influx of neutrophils results in tissue damage that is detrimental to the patient. Accordingly, limiting neutrophil recruitment or neutrophil activation in the lung may benefit patients with ARDS, thereby improving outcomes. Our laboratory is interested in the signaling pathways that are activated in neutrophils during acute inflammation. One such pathway is the evolutionary conserved mitogen activated protein kinase (MAPK) cascade. Exposure of neutrophils to inflammatory mediators, such as lipopolysaccharide (LPS) or chemokines (e.g. Interleukin 8--IL-8), activates components of the MAPK cascade leading to the expression and release of pro-inflammatory proteins. Our laboratory has previously examined the signaling pathways by which LPS activates the MAPK c-Jun NH2-terminal kinase (JNK) in neutrophils and have shown that JNK regulates neutrophil recruitment to the lung after exposure to LPS. Although we continue to examine pathways leading to JNK activation in LPS-stimulated neutrophils, our laboratory is currently focusing on the role of the proteoglycan syndecan-4 in regulating the activation of JNK in neutrophils exposed to the chemokine IL-8. IL-8 is a major attractant for neutrophil migration and is highly expressed at sites of acute inflammation. In addition, IL-8 binds to syndecan-4 suggesting that syndecan-4 is uniquely positioned to regulate IL-8-induced signaling in neutrophils. We plan to examine the upstream signaling events that are regulated by syndecan-4 in the IL-8-induced pathway leading to JNK activation using biochemical and in vitro and in vivo genetic knockdown strategies. Our hopes are that these studies will further elucidate the mechanisms by which IL-8 activates JNK in neutrophils, and therefore neutrophil migration, and will provide potential modalities to control the inflammatory response. In addition, the lab is beginning to examine the mechanisms by which the renin angiotenisn system regulates neutrophil influx during acute inflammation. Currently, angiotensin converting enzyme inhibitors (ACE inhibitors) are widely used and are effective in patients with cardiovascular disease. In addition to their effect on blood pressure and cardiac function, however, ACE inhibitors decrease neutrophil recruitment to inflammatory sites. The goal of this project is to determine the mechanisms by which ACE-I decrease neutrophil recruitment and specifically the signaling pathways that are regulated by the RAS in neutrophils.

Publications

  • Young SK, Arndt PG. c-Jun N-terminal kinase regulates lipopolysaccharide-induced pulmonary mononuclear cell recruitment via CCL2. Exp Lung Res. 2009;35(8):682-700.
  • Zemans RL, Arndt PG. Tec kinases regulate actin assembly and cytokine expression in LPS-stimulated human neutrophils via JNK activation. Cell Immunol. 2009; 258(1):90-97.
  • Fessler, MB, Arndt PG, Just I, Nick JA, Malcolm KC, Worthen GS. Dual role for RhoA in suppression and induction of cytokines in the human neutrophil. Blood 2007, Feb 1, 109(3):1248-1256. PMCID: PMC1785129
  • Arndt PG,Young SK, Poch, KR, Nick JA, Falk S, Schrier RW, Worthen GS. Systemic inhibition of the angiotensin-converting enzyme limits lipopolysaccaride-induced lung neutrophil recruitment through both bradykinin and angiotensin II-regulated pathways. J Immunol 2006 Nov 15, 177(10):7233-7241.
  • Jeyaseelan S, Young SK, Yamamoto M, Arndt PG, Akira S, Kolls JK, and Worthen GS. Toll/IL-1R domain-containing adaptor protein (TIRAP) is a critical mediator of antibacterial defense in the lung against Klebsiella pneumoniae but not Pseuodomonas aeruginosa. J Immunol 2006 Jul 1, 177(1): 538-47.
  • Arndt PG, Young SK, and Worthen GS. Regulation of lipopolysaccharide-induced lung inflammation by plasminogen activator inhibitor-1 through a c-Jun N-terminal kinase mediated pathway. J Immunol 2005 Sept 15, 175(6):4049-59.
  • Arndt PG, Young SK, Lieber JG, Fessler MB, Nick JA, Worthen GS. Inhibition of c-Jun-N-terminal kinase limits lipopolysaccaride-induced pulmonary neutrophil influx. Am J Resp Crit Care Med. 2005 May 1, 171(9)978-86.

For a comprehensive list of Dr. Arndt's recent publications, refer to PubMed, a service provided by the National Library of Medicine.

Clinical

Clinics

Center for Lung Science and Health

Board Certifications

  • Pulmonary Medicine
  • Critical Care Medicine

Clinical Interests

General Pulmonary, Pulmonary complications after hematopoietic stem cell transplant

Hospital Privileges

Fairview Lakes Medical Center; Fairview Northland Medical Center; Fairview Ridges Hospital; Fairview Southdale Hospital; University of Minnesota Medical Center, Fairview