Hyaluronan deposition and correlation with inflammation in a murine ovalbumin model of asthma.
Asthma is a chronic inflammatory disease of the airways characterized by airway remodeling, which includes changes in the extracellular matrix (ECM). However the role of the ECM in mediating these changes is poorly understood. Hyaluronan (HA), a major component of the ECM, has been implicated in asthma as well as in many other biological processes. Our study investigates the processes involved in HA synthesis, deposition, localization and degradation during an acute and chronic murine model of ovalbumin (OVA)-induced allergic pulmonary inflammation. Mice were sensitized, challenged to OVA and sacrificed at various time points during an 8-week challenge protocol. Bronchoalveolar lavage (BAL) fluids, blood, and lung tissue were collected for study. RNA, HA, protein and histopathology were analyzed. Analyses of lung sections and BAL fluids revealed an early deposition and an increase in HA levels within 24 h of antigen exposure. HA levels peaked at day 8 in BAL, while inflammatory cell recovery peaked at day 6. Hyaluronan synthase (HAS)1 and HAS2 on RNA levels peaked within 2 h of antigen exposure, while hyaluronidase (HYAL)1 and HYAL2 on RNA levels decreased. Both inflammatory cell infiltrates and collagen deposition co-localized with HA deposition within the lungs. These data support a role for HA in the pathogenesis of inflammation and airway remodeling in a murine model of asthma. HA deposition appears largely due to up regulation of HAS1 and HAS2. In addition, HA appears to provide the scaffolding for inflammatory cell accumulation as well as for new collagen synthesis and deposition.
Department of Pathobiology, Lerner Research Institute, Cleveland, OH, United States.
Georgiana
G
Cheng
Shadi
S
Swaidani
Manisha
M
Sharma
Mark E
ME
Lauer
Vincent C
VC
Hascall
Mark A
MA
Aronica
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D047093:Eosinophil Major Basic Protein / Q000378:metabolism / Q000494:pharmacology; D004804:Eosinophils / Q000378:metabolism / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D014453:Glucuronosyltransferase / Q000235:genetics; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000235:genetics; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D014611:Vaccination
D058851:GPI-Linked Proteins; D006820:Hyaluronic Acid; D010047:Ovalbumin; D003094:Collagen; D014453:Glucuronosyltransferase; C491099:Has2 protein, mouse; C491356:Has3 protein, mouse; D000076002:Hyaluronan Synthases; D047093:Eosinophil Major Basic Protein; C469220:Hyal1 protein, mouse; C469221:Hyal2 protein, mouse; D006821:Hyaluronoglucosaminidase
J Biol Chem. 2009 Feb 20;284(8):5313-23
19075022
J Biol Chem. 2009 Feb 20;284(8):5299-312
19088077
J Exp Med. 2005 Jun 20;201(12):1869-73
15967817
Curr Opin Allergy Clin Immunol. 2001 Feb;1(1):85-93
11964675
J Clin Invest. 2003 Feb;111(3):291-7
12569150
Am J Physiol Lung Cell Mol Physiol. 2009 Sep;297(3):L401-10
19561139
FASEB J. 2001 Oct;15(12):2179-86
11641244
J Immunol. 1999 Nov 1;163(9):5116-24
10528218
Int J Exp Pathol. 2000 Jun;81(3):173-82
10971738
Chest. 1995 Mar;107(3 Suppl):111S-117S
7874987
Curr Opin Cell Biol. 1999 Oct;11(5):634-40
10508658
Am J Respir Crit Care Med. 1999 Aug;160(2):725-9
10430752
Chem Rev. 2006 Mar;106(3):818-39
16522010
Am J Respir Crit Care Med. 2004 Mar 1;169(5):587-95
14617509
J Biol Chem. 2007 Dec 21;282(51):36777-81
17981795
Am J Respir Cell Mol Biol. 2004 Jul;31(1):92-9
14764429
J Biol Chem. 2002 Feb 15;277(7):4581-4
11717316
Science. 2002 Apr 5;296(5565):155-8
11935029
Allergol Int. 2007 Dec;56(4):321-9
17965575
J Biol Chem. 2002 Feb 15;277(7):4585-8
11717315
Thromb Haemost. 2007 Aug;98(2):287-95
17721609
J Biol Chem. 2008 Sep 19;283(38):26283-96
18644783
J Allergy Clin Immunol. 1991 Oct;88(4):649-60
1918730
Curr Allergy Asthma Rep. 2008 Jul;8(4):357-66
18606090
Cell Biol Int. 2001;25(8):735-9
11482897
Annu Rev Cell Dev Biol. 2007;23:435-61
17506690
J Immunol. 1995 Apr 15;154(8):4073-80
7535820
J Intern Med. 1997 Jul;242(1):27-33
9260563
Blood. 2004 Jan 15;103(2):740-2
14504094
J Leukoc Biol. 2000 Feb;67(2):149-59
10670574
Am J Respir Cell Mol Biol. 2000 Oct;23(4):444-51
11017908
Clin Exp Pharmacol Physiol. 2001 Mar;28(3):233-6
11236132
Biochem J. 1978 Aug 1;173(2):565-8
697736