Abstract

and specific aims): Leukotrienes (LTs) are potent mediators implicated in the pathogenesis of inflammatory lung diseases, and new pharmacologic agents that inhibit LT synthesis or actions will soon be available for the treatment of asthma. It is generally assumed that inflammatory cascades have evolved for the purpose of host defense against microbial invasion, yet little is known about the possible importance of endogenous LTs in mediating the host response to infection. This applicator hypothesize that 1) endogenous LTs play an integral role in the host response to pulmonary infection, and 2) exogenous LTs exert pharmacologic actions which augment this response. These hypotheses will be tested by a series of in vivo and in vitro experiments designed to address the following Specific Aims.
Aim 1 will ascertain the roles of specific endogenous 5-LO products in the host response to K. pneumonia, using pharmacologic agents which inhibit LT synthesis or actions.
Aim 2 will determine the kinetics, profile, and cellular sources of LTs produced in the murine lung during the course of Klebsiella pneumonia.
Aim 3 will determine the molecular mechanisms by which specific 5-LO products augment phagocytosis and killing of K. pneumonia in AMs and PMNs.
Aim 4 will test the potential of intrapulmonary LT administration to augment the host response to Klebsiella challenge.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL058897-02
Application #
2735406
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1997-07-10
Project End
2000-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Zas?ona, Zbigniew; Scruggs, Anne M; Peters-Golden, Marc et al. (2016) Protein kinase A inhibition of macrophage maturation is accompanied by an increase in DNA methylation of the colony-stimulating factor 1 receptor gene. Immunology 149:225-37
Bourdonnay, Emilie; Zas?ona, Zbigniew; Penke, Loka Raghu Kumar et al. (2015) Transcellular delivery of vesicular SOCS proteins from macrophages to epithelial cells blunts inflammatory signaling. J Exp Med 212:729-42
Zaslona, Zbigniew; Peters-Golden, Marc (2015) Prostanoids in Asthma and COPD: Actions, Dysregulation, and Therapeutic Opportunities. Chest 148:1300-1306
Degraaf, Angela Juliette; Zas?ona, Zbigniew; Bourdonnay, Emilie et al. (2014) Prostaglandin E2 reduces Toll-like receptor 4 expression in alveolar macrophages by inhibition of translation. Am J Respir Cell Mol Biol 51:242-50
Brogliato, Ariane R; Moor, Andrea N; Kesl, Shannon L et al. (2014) Critical role of 5-lipoxygenase and heme oxygenase-1 in wound healing. J Invest Dermatol 134:1436-1445
Monteiro, Ana Paula T; Soledade, Erico; Pinheiro, Carla S et al. (2014) Pivotal role of the 5-lipoxygenase pathway in lung injury after experimental sepsis. Am J Respir Cell Mol Biol 50:87-95
Zas?ona, Zbigniew; Okunishi, Katsuhide; Bourdonnay, Emilie et al. (2014) Prostaglandin E? suppresses allergic sensitization and lung inflammation by targeting the E prostanoid 2 receptor on T cells. J Allergy Clin Immunol 133:379-87
Zas?ona, Zbigniew; Przybranowski, Sally; Wilke, Carol et al. (2014) Resident alveolar macrophages suppress, whereas recruited monocytes promote, allergic lung inflammation in murine models of asthma. J Immunol 193:4245-53
O'Brien, E; Bergin, I L; Dolinoy, D C et al. (2014) Perinatal bisphenol A exposure beginning before gestation enhances allergen sensitization, but not pulmonary inflammation, in adult mice. J Dev Orig Health Dis 5:121-31
Wang, Zhuo; Filgueiras, Luciano Ribeiro; Wang, Soujuan et al. (2014) Leukotriene B4 enhances the generation of proinflammatory microRNAs to promote MyD88-dependent macrophage activation. J Immunol 192:2349-56

Showing the most recent 10 out of 61 publications