| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 142, 273-283, Copyright © 1993 by American Society for Investigative Pathology
REGULAR ARTICLES |
LF Brown, N Lanir, J McDonagh, K Tognazzi, AM Dvorak and HF Dvorak
Department of Pathology, Beth Israel Hospital, Boston, MA 02215.
In healing wounds and many solid tumors, locally increased microvascular permeability results in extravasation of fibrinogen and its extravascular coagulation to form a fibrin gel, with concomitant covalent cross-linking of fibrin by factor XIIIa. Subsequently, inflammatory cells, fibroblasts, and endothelial cells migrate into the gel and organize it into granulation tissue and later into mature collagenous connective tissue. To gain insight into some of the cell migration events associated with these processes, we developed a quantitative in vitro assay that permits the study of fibroblast migration in fibrin gels. Early passage human or rat fibroblasts were allowed to attach to tissue culture dishes and then were overlaid with a thin layer of fibrinogen that was clotted with thrombin. Fibroblasts began to migrate upwards into the fibrin within 24 hours and their numbers and the distance migrated were quantified over several days. The extent of fibroblast migration was affected importantly by the nature of the fibrin clot. Fibroblasts migrated optimally into gels prepared from fibrinogen at concentrations of -3 mg/ml; ie, near normal plasma fibrinogen levels. Migration was greatly enhanced by extensive cross-linking of the fibrin alpha-chains by factor XIIIa, as occurs when clotting takes place in vivo. When fibrinogen was clotted in Dulbecco's modified Eagle's medium, gamma-chains were cross-linked, but alpha-chain cross-linking was strikingly inhibited, and fibroblasts migrated poorly. Gels prepared from factor XIII-depleted fibrinogen exhibited neither alpha-nor gamma-chain cross-linking and did not support fibroblast migration. Further purification of fibrinogen by anion exchange high pressure liquid chromatography depleted fibrinogen of fibronectin, plasminogen, and other impurities; this purified fibrinogen clotted to form fibrin gels that supported reproducible fibroblast migration.
This article has been cited by other articles:
 |
|
 |
|
  A. G. McDonald, K. Yang, H. R. Roberts, D. M. Monroe, and M. Hoffman Perivascular tissue factor is down-regulated following cutaneous wounding: implications for bleeding in hemophilia Blood, February 15, 2008; 111(4): 2046 - 2048. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Tse, A. W. H. Chan, K.-H. Yu, A. D. King, K.-T. Wong, G. G. Chen, R. K. Y. Tsang, and A. B. W. Chan Strong Immunohistochemical Expression of Vascular Endothelial Growth Factor Predicts Overall Survival in Head and Neck Squamous Cell Carcinoma Ann. Surg. Oncol., December 1, 2007; 14(12): 3558 - 3565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nahrendorf, K. Hu, S. Frantz, F. A. Jaffer, C.-H. Tung, K.-H. Hiller, S. Voll, P. Nordbeck, D. Sosnovik, S. Gattenlohner, et al. Factor XIII Deficiency Causes Cardiac Rupture, Impairs Wound Healing, and Aggravates Cardiac Remodeling in Mice With Myocardial Infarction Circulation, March 7, 2006; 113(9): 1196 - 1202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. de Giorgio-Miller, S. Bottoms, G. Laurent, P. Carmeliet, and S. Herrick Fibrin-Induced Skin Fibrosis in Mice Deficient in Tissue Plasminogen Activator Am. J. Pathol., September 1, 2005; 167(3): 721 - 732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Zamboni, M. De Mattei, A. Ongaro, L. Fogato, S. Carandina, M. De Palma, S. Tognazzo, G. L. Scapoli, M. L. Serino, A. Caruso, et al. Factor XIII Contrasts the Effects of Metalloproteinases in Human Dermal Fibroblast Cultured Cells Vascular and Endovascular Surgery, September 1, 2004; 38(5): 431 - 438. [Abstract] [PDF]
|
|
|
|
|
|
V. Fontaine, Z. Touat, E. M. Mtairag, R. Vranckx, L. Louedec, X. Houard, B. Andreassian, U. Sebbag, T. Palombi, M.-P. Jacob, et al. Role of Leukocyte Elastase in Preventing Cellular Re-Colonization of the Mural Thrombus Am. J. Pathol., June 1, 2004; 164(6): 2077 - 2087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. O. Duan and P. J. Simpson-Haidaris Functional Analysis of Interleukin 6 Response Elements (IL-6REs) on the Human {gamma}-Fibrinogen Promoter: BINDING OF HEPATIC Stat3 CORRELATES NEGATIVELY WITH TRANSACTIVATION POTENTIAL OF TYPE II IL-6REs J. Biol. Chem., October 17, 2003; 278(42): 41270 - 41281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. F. Dvorak How Tumors Make Bad Blood Vessels and Stroma Am. J. Pathol., June 1, 2003; 162(6): 1747 - 1757. [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Palumbo, J. M. Potter, L. S. Kaplan, K. Talmage, D. G. Jackson, and J. L. Degen Spontaneous Hematogenous and Lymphatic Metastasis, but not Primary Tumor Growth or Angiogenesis, Is Diminished in Fibrinogen-deficient Mice Cancer Res., December 1, 2002; 62(23): 6966 - 6972. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Hotary, I. Yana, F. Sabeh, X.-Y. Li, K. Holmbeck, H. Birkedal-Hansen, E. D. Allen, N. Hiraoka, and S. J. Weiss Matrix Metalloproteinases (MMPs) Regulate Fibrin-invasive Activity via MT1-MMP-dependent and -independent Processes J. Exp. Med., January 28, 2002; 195(3): 295 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. Drew, H. Liu, J. M. Davidson, C. C. Daugherty, and J. L. Degen Wound-healing defects in mice lacking fibrinogen Blood, June 15, 2001; 97(12): 3691 - 3698. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. DEGEN, A. F. DREW, J. S. PALUMBO, K. W. KOMBRINCK, J. A. BEZERRA, M. J. S. DANTON, K. HOLMBACK, and T. T. SUH Genetic Manipulation of Fibrinogen and Fibrinolysis in Mice Ann. N.Y. Acad. Sci., June 1, 2001; 936(1): 276 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A.F. CLARK Fibrin and Wound Healing Ann. N.Y. Acad. Sci., June 1, 2001; 936(1): 355 - 367. [Full Text] [PDF]
|
|
|
|
|
|
J. A. WILBERDING, V. A. PLOPLIS, L. McLENNAN, Z. LIANG, I. CORNELISSEN, M. FELDMAN, M. E. DEFORD, E. D. ROSEN, and F. J. CASTELLINO Development of Pulmonary Fibrosis in Fibrinogen-Deficient Mice Ann. N.Y. Acad. Sci., June 1, 2001; 936(1): 542 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. AMRANI, J. P. DIORIO, and Y. DELMOTTE Wound Healing: Role of Commercial Fibrin Sealants Ann. N.Y. Acad. Sci., June 1, 2001; 936(1): 566 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. L. HADDEN and C. A. HENKE Induction of Lung Fibroblast Apoptosis by Soluble Fibronectin Peptides Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): 1553 - 1560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. A. Ploplis, J. Wilberding, L. McLennan, Z. Liang, I. Cornelissen, M. E. DeFord, E. D. Rosen, and F. J. Castellino A Total Fibrinogen Deficiency Is Compatible with the Development of Pulmonary Fibrosis in Mice Am. J. Pathol., September 1, 2000; 157(3): 703 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Swaisgood, E. L. French, C. Noga, R. H. Simon, and V. A. Ploplis The Development of Bleomycin-Induced Pulmonary Fibrosis in Mice Deficient for Components of the Fibrinolytic System Am. J. Pathol., July 1, 2000; 157(1): 177 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ikari, K. Fujikawa, K. O. Yee, and S. M. Schwartz alpha 1-Proteinase Inhibitor, alpha 1-Antichymotrypsin, or alpha 2-Macroglobulin Is Required for Vascular Smooth Muscle Cell Spreading in Three-dimensional Fibrin Gel J. Biol. Chem., April 21, 2000; 275(17): 12799 - 12805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Raymond, A. C. Desfaits, D. Roy, and J. P. Muizelaar Fibrinogen and Vascular Smooth Muscle Cell Grafts Promote Healing of Experimental Aneurysms Treated by Embolization • Editorial Comment Stroke, August 1, 1999; 30(8): 1657 - 1664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G. Sitrin, P. M. Pan, S. Srikanth, and R. F. Todd III Fibrinogen Activates NF-{kappa}B Transcription Factors in Mononuclear Phagocytes J. Immunol., August 1, 1998; 161(3): 1462 - 1470. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Guadiz, L. A. Sporn, and P. J. Simpson-Haidaris Thrombin Cleavage-Independent Deposition of Fibrinogen in Extracellular Matrices Blood, October 1, 1997; 90(7): 2644 - 2653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Guadiz, L. A. Sporn, R. A. Goss, S. O. Lawrence, V. J. Marder, and P. J. Simpson-Haidaris Polarized Secretion of Fibrinogen by Lung Epithelial Cells Am. J. Respir. Cell Mol. Biol., July 1, 1997; 17(1): 60 - 69. [Abstract] [Full Text]
|
|
|
|
 |
|
 D Greiling and R. Clark Fibronectin provides a conduit for fibroblast transmigration from collagenous stroma into fibrin clot provisional matrix J. Cell Sci., January 4, 1997; 110(7): 861 - 870. [Abstract] [PDF]
|
|
|
|
 |
|
 T T Suh, K Holmback, N J Jensen, C C Daugherty, K Small, D I Simon, S Potter, and J L Degen Resolution of spontaneous bleeding events but failure of pregnancy in fibrinogen-deficient mice. Genes & Dev., August 15, 1995; 9(16): 2020 - 2033. [Abstract] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
