Kurdowska, Anna K., Ph.D.
1986, Ph.D. Biochemistry, Jagiellonian Univ., Cracow, Poland
1980, M.S. Biochemistry, Jagiellonian Univ., Cracow, Poland
Innate immunity and inflammatory response; Acute phase proteins; proteinase inhibitors (production, purification, biochemical analysis; stimulation by and of inflammatory cytokines); Interleukin-1 (IL-1), tumor necrosis factor (TNF), and interleukin-6 (IL-6) and other cytokines - role in disease; Interleukin-8 (IL-8) and related chemokines; production; biological activity; regulation of function; Inflammatory response in the lung related to the acute lung injury / acute respiratory syndrome (ALI/ARDS), tuberculosis, and asthma; Analysis of inflammatory mediators present in samples from patients with these and other inflammatory diseases.
- Course of inflammatory response in lung disease.
- Regulation of innate immunity in lung inflammation.
- Neutrophils, endothelial, and epithelial cells in the lung - activation and apoptosis.
- IgG receptors (FcgammaRs), and TLR4 - regulation and signaling in the lung.
Interleukin-8 (IL-8) belongs to a family of hormone-like small proteins functioning as mediators of the body response in different diseases. IL-8 is responsible for attracting white blood cells to the tissue, e.g., the lung, and activating them. The acute lung injury / acute respiratory distress syndrome (ALI/ARDS), a very serious lung disease, is associated with the presence of IL-8 in the lung. IL-8 is also involved in the pathogenesis of several other diseases including asthma, tuberculosis, and malignant melanoma.
The acute lung injury / acute respiratory distress syndrome (ALI/ARDS) can be described as a complex clinical syndrome that results in significant impairment of lung function. Interleukin-8 (IL-8; a hormone-like substance) is one of the major mediators of lung inflammation in ALI/ARDS. The results of my studies suggest that naturally occurring antibodies (autoantibodies) directed against IL-8 may potentiate inflammatory process ongoing in the lungs of patients with ALI/ARDS. We also have found that a human plasma enzyme inhibitor, called alpha-2-macroglobulin (alpha-2-M), acts as IL-8 carrier, and regulates IL-8 function in the lung. We are currently defining the mechanisms by which these factors manifest their activities both at the cellular and molecular levels. In addition, we are investigating the role of IL-8 and in other lung diseases, including asthma and TB. We are also exploring function of IL-8 in melanoma.
Selected Papers and Abstracts:
- Kurdowska A, Krupa A. Blockade of interleukin-6 in murine sepsis revisited: is there an indication for a new therapy in human patients? Crit. Care Med. 39:1582-1583, 2011.
- Wu Z, Sawamura T, Kurdowska AK, Ji HL, Idell S, Fu J. LOX-1 Deletion Improves Neutrophil Responses, Enhances Bacterial Clearance, and Reduces Lung Injury in a Murine Polymicrobial Sepsis Model. Infect. Immun. 79:2865-2870, 2011.
- Fudala R, Allen TC, Krupa A, Cagle PT, Nash S, Gryczynski Z, Gryczynski I, Kurdowska AK. Increased levels of nuclear factor κB and Fos-related antigen 1 in lung tissues from patients with acute respiratory distress syndrome. Arch Pathol Lab Med. 135:647-654, 2011.
- Fudala R, Krupa A, Stankowska D, Allen TC, Kurdowska AK. Does activation of the FcgammaRIIa play a role in the pathogenesis of the acute lung injury/acute respiratory distress syndrome? Clin. Sci. (Lond). 118:519-526, 2010.
- Kurdowska AK, Krupa A, Fudala R. Delay of LPS-induced acute lung injury resolution by soluble immune complexes is neutrophil dependent. Shock 33:106; author reply 106-7. 2010.
- Komissarov AA, Mazar AP, Koenig K, Kurdowska AK, Idell S. Regulation of intrapleural fibrinolysis by urokinase-alpha-macroglobulin complexes in tetracycline-induced pleural injury in rabbits. Am. J. Physiol. Lung Cell. Mol. Physiol. 297:L568-L577. 2009.
- Krupa A, Fudala R, Stankowska D, Loyd T, Allen TC, Matthay MA, Gryczynski Z, Gryczynski I, Mettikolla YV, Kurdowska AK. Anti-chemokine autoantibody:chemokine immune complexes activate endothelial cells via IgG receptors. Am. J. Respir. Cell Mol. Biol. 41:155-169, 2009.
- Fudala R, Krupa A, Stankowska D, Allen TC, Kurdowska AK. Anti-interleukin-8 autoantibody:interleukin-8 immune complexes in acute lung injury/acute respiratory distress syndrome. Clin Sci (Lond). 2008 Mar;114(6):403-12.
- Krupa A, Walencka MJ, Shrivastava V, Loyd T, Fudala R, Frevert CW, Martin TR, Kurdowska AK. Anti-KC autoantibody:KC complexes cause severe lung inflammation in mice via IgG receptors. Am J Respir Cell Mol Biol. 2007 Nov;37(5):532-43.
- Fudala R, Krupa A, Matthay MA, Allen TC, Kurdowska AK.
Anti-IL-8 autoantibody:IL-8 immune complexes suppress spontaneous apoptosis of neutrophils. Am J Physiol Lung Cell Mol Physiol. 2007 Aug;293(2):L364-74.
- T.C.Allen, R.Fudala, S.Nash, A.Kurdowska. Anti-interleukin-8 Autoantibody:Interleukin-8 Immune Complexes Visualized by Laser Confocal Microscopy in Injured Lung. Co-localization with FcγRIIa in Lung Tissues from Patients with Acute Respiratory Distress Syndrome. Arch. Pathol. Lab. Med.131:452-456, 2007.
- Krupa A, Kato H, Matthay MA, Kurdowska AK. Proinflammatory activity of anti-IL-8 autoantibody:IL-8 complexes in alveolar edema fluid from patients with acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2004 Jun;286(6):L1105-13. Epub 2004 Jan 16.
- Kurdowska AK. Can inflammatory mediators affect fibrinolysis in the pleural space? Clin Sci (Lond). 2003 Nov;105(5):541-3.
- Kurdowska AK. Unusual causes of acute pulmonary oedema. Clin Sci (Lond). 2003 Mar;104(3):265-6.
- Kurdowska AK, Noble JM, Adcock JE. Interleukin-8 and anti-interleukin-8 autoantibodies in gingival crevicular fluid from patients with periodontitis. J. of Periodont. Res. 38:73-78, 2003.
- Kurdowska A, Miller EJ, Krupa A, Noble JM, Sakao Y. Monoclonal antibodies to rabbit alpha-2-macroglobulin and their use in a sensitive ELISA assay. J. Immunol. Methods 270:147-153, 2002.
- Kurdowska A, Noble JM, Grant IS, Robertson CR, Haslett C, Donnelly SC. Anti-interleukin-8 autoantibodies in patients at risk for acute respiratory distress syndrome. Crit. Care Med. 30:2335 2337, 2002.
- Kurdowska AK, Geiser TK, Alden SM, Dziadek BR, Noble JM, Nuckton TJ, Matthay MA. Activity of pulmonary edema fluid interleukin-8 bound to alpha(2)-macroglobulin in patients with acute lung injury. Am. J. Physiol. 282:L1092-1098, 2002.
- Kurdowska AK, Noble JM, Griffith DE. The Effect of The effect of azithromycin and clarithromycin on ex vivo interleukin-8 (IL-8) release from whole blood and IL-8 production by human alveolar macrophages. Journal of Antimicrobial Chemotherapy 47:867-870, 2001.
- Kurdowska AK, Noble JM, Steinberg KP, Ruzinski JT, Hudson LD, Martin TR. Anti-interleukin 8 autoantibody: interleukin 8 complexes in the acute respiratory distress syndrome. Relationship between the complexes and clinical disease activity. Am.J.Respir.Crit. Care Med. 163:463-468, 2001.