Regulation of proteinase inhibitors in acute inflammatory lung injury in rats

T. S. Gipson, N. Bless, L. Crouch, M. R. Bleavins, W. Tefera, K. J. Johnson, P. A. Ward

Research output: Contribution to journalArticle

Abstract

Proteinase inhibitors such as tissue inhibitor of metalloproteinase-2 (TIMP-2) and secretory leukocyte proteinase inhibitor (SLPI), have been implicated in a variety of pathogenic processes, including inflammatory lung diseases. The regulation of TIMP-2 and SLPI activities during inflammatory lung diseases is important for the prevention of tissue damage. To investigate the regulatory roles of these inhibitors in acute lung injury, the genes for rat TIMP-2 and SLPI were PCR-cioned. We also characterized transcriptional expression and developed polyclonal antibodies for both proteins. For SLPI, which had not previously been cloned, there was 67% and 91% identity with the amino acid sequences for human and murine SLPI, respectively. Following intrapulmonary deposition of immune complexes into rat lungs, upregulation of mRNA and protein expression in bronchoalveolar lavage (BAL) fluids of both inhibitors were detected. Intratracheal administration of anti-TIMP-2 or anti-SLPI antibodies resulted in significantly enhanced accumulation of neutrophils in BAL fluids and increased lung injury, as measured by the leakage of 125I labeled-albumin into lung parenchyma. Neither anti-TIMP-2 nor anti-SLPI caused significantly elevated levels of chemotactic activity, TNF-∝ or C-X-C chemokine content in BAL fluids. These data suggest that endogenous TIMP-2 and SLPI regulate the intrapulmonary recruitment of neutrophils and the intensity of inflammatory lung damage.

Original languageEnglish (US)
Pages (from-to)A793
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

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Acute Lung Injury
proteinase inhibitors
Rats
Tissue Inhibitor of Metalloproteinase-2
Peptide Hydrolases
leukocytes
lungs
metalloproteinases
Leukocytes
rats
Bronchoalveolar Lavage Fluid
Pulmonary diseases
Lung
respiratory tract diseases
Lung Diseases
Fluids
neutrophils
CXC Chemokines
antigen-antibody complex
Neutrophil Infiltration

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Gipson, T. S., Bless, N., Crouch, L., Bleavins, M. R., Tefera, W., Johnson, K. J., & Ward, P. A. (1998). Regulation of proteinase inhibitors in acute inflammatory lung injury in rats. FASEB Journal, 12(5), A793.

Regulation of proteinase inhibitors in acute inflammatory lung injury in rats. / Gipson, T. S.; Bless, N.; Crouch, L.; Bleavins, M. R.; Tefera, W.; Johnson, K. J.; Ward, P. A.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998, p. A793.

Research output: Contribution to journalArticle

Gipson, TS, Bless, N, Crouch, L, Bleavins, MR, Tefera, W, Johnson, KJ & Ward, PA 1998, 'Regulation of proteinase inhibitors in acute inflammatory lung injury in rats', FASEB Journal, vol. 12, no. 5, pp. A793.
Gipson TS, Bless N, Crouch L, Bleavins MR, Tefera W, Johnson KJ et al. Regulation of proteinase inhibitors in acute inflammatory lung injury in rats. FASEB Journal. 1998 Mar 20;12(5):A793.
Gipson, T. S. ; Bless, N. ; Crouch, L. ; Bleavins, M. R. ; Tefera, W. ; Johnson, K. J. ; Ward, P. A. / Regulation of proteinase inhibitors in acute inflammatory lung injury in rats. In: FASEB Journal. 1998 ; Vol. 12, No. 5. pp. A793.
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