Skip to main content
NCBI home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1995 Mar;4(2):133–137. doi: 10.1155/S0962935195000238

Inhibition of neutrophil migration by a selective inhibitor of matrix metalloproteinase: analysis by intravital microscopy

T Oda 1,3, M Katori 1,✉, K Hatanaka 1, Y Nagai 2
PMCID: PMC2365620  PMID: 18475630

Abstract

Observation of the microcirculation of the hamster cheek pouch by intravital microscopy revealed five steps of neutrophil migration from the venules after topical application of leukotriene B4 to the microvasculature: rolling along the venular wall (Step 1), adhesion to it (Step 2), disappearance from the vascular lumen (Step 3), presence between the endothelial cells and the subendothelial basement membrane (Step 4) and passage through the basement membrane (Step 5). The present study was performed to examine whether a metalloproteinase inhibitor inhibits neutrophil migration at any of the above five steps. Chymostatin and leupeptin did not inhibit any of these five steps. In contrast, FN-439, a selective inhibitor of matrix metalloproteinase, reduced the number of neutrophils in the perivascular space without affecting Steps 1 to 3. It was concluded that neutrophils may use metalloproteinase (collagenase/gelatinase) to penetrate the subendothelial basement membrane.

Full Text

The Full Text of this article is available as a PDF (455.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbassi O., Lane C. L., Krater S., Kishimoto T. K., Anderson D. C., McIntire L. V., Smith C. W. Canine neutrophil margination mediated by lectin adhesion molecule-1 in vitro. J Immunol. 1991 Oct 1;147(7):2107–2115. [PubMed] [Google Scholar]
  2. Cybulsky M. I., McComb D. J., Movat H. Z. Protein synthesis dependent and independent mechanisms of neutrophil emigration. Different mechanisms of inflammation in rabbits induced by interleukin-1, tumor necrosis factor alpha or endotoxin versus leukocyte chemoattractants. Am J Pathol. 1989 Jul;135(1):227–237. [PMC free article] [PubMed] [Google Scholar]
  3. Huber A. R., Weiss S. J. Disruption of the subendothelial basement membrane during neutrophil diapedesis in an in vitro construct of a blood vessel wall. J Clin Invest. 1989 Apr;83(4):1122–1136. doi: 10.1172/JCI113992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Kigasawa K., Murata H., Morita Y., Odake S., Suda E., Shimizu I., Morikawa T., Nagai Y. Inhibition of corneal ulceration by tetrapeptidyl hydroxamic acid. Jpn J Ophthalmol. 1995;39(1):35–42. [PubMed] [Google Scholar]
  5. Kishimoto T. K., Warnock R. A., Jutila M. A., Butcher E. C., Lane C., Anderson D. C., Smith C. W. Antibodies against human neutrophil LECAM-1 (LAM-1/Leu-8/DREG-56 antigen) and endothelial cell ELAM-1 inhibit a common CD18-independent adhesion pathway in vitro. Blood. 1991 Aug 1;78(3):805–811. [PubMed] [Google Scholar]
  6. Malech H. L., Root R. K., Gallin J. I. Structural analysis of human neutrophil migration. Centriole, microtubule, and microfilament orientation and function during chemotaxis. J Cell Biol. 1977 Dec;75(3):666–693. doi: 10.1083/jcb.75.3.666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Nagai K., Katori M. Possible changes in the leukocyte membrane as a mechanism of leukocyte adhesion to the venular walls induced by leukotriene B4 and fMLP in the microvasculature of the hamster cheek pouch. Int J Microcirc Clin Exp. 1988 Nov;7(4):305–314. [PubMed] [Google Scholar]
  8. Oda T., Katori M., Hatanaka K., Yamashina S. Five steps in leukocyte extravasation in the microcirculation by chemoattractants. Mediators Inflamm. 1992;1(6):403–409. doi: 10.1155/S0962935192000619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Oda T., Katori M. Inhibition site of dexamethasone on extravasation of polymorphonuclear leukocytes in the hamster cheek pouch microcirculation. J Leukoc Biol. 1992 Sep;52(3):337–342. doi: 10.1002/jlb.52.3.337. [DOI] [PubMed] [Google Scholar]
  10. Odake S., Morita Y., Morikawa T., Yoshida N., Hori H., Nagai Y. Inhibition of matrix metalloproteinases by peptidyl hydroxamic acids. Biochem Biophys Res Commun. 1994 Mar 30;199(3):1442–1446. doi: 10.1006/bbrc.1994.1392. [DOI] [PubMed] [Google Scholar]
  11. Odake S., Okayama T., Obata M., Morikawa T., Hattori S., Hori H., Nagai Y. Vertebrate collagenase inhibitor. II. Tetrapeptidyl hydroxamic acids. Chem Pharm Bull (Tokyo) 1991 Jun;39(6):1489–1494. doi: 10.1248/cpb.39.1489. [DOI] [PubMed] [Google Scholar]
  12. Romanic A. M., Madri J. A. The induction of 72-kD gelatinase in T cells upon adhesion to endothelial cells is VCAM-1 dependent. J Cell Biol. 1994 Jun;125(5):1165–1178. doi: 10.1083/jcb.125.5.1165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Werb Z., Tremble P. M., Behrendtsen O., Crowley E., Damsky C. H. Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression. J Cell Biol. 1989 Aug;109(2):877–889. doi: 10.1083/jcb.109.2.877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Wright D. G., Gallin J. I. Secretory responses of human neutrophils: exocytosis of specific (secondary) granules by human neutrophils during adherence in vitro and during exudation in vivo. J Immunol. 1979 Jul;123(1):285–294. [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES