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Fibrinogen induces endothelial cell permeability by increasing F‐actin formation
Author(s) -
Lominadze David,
Tyagi Neetu,
Tyagi Suresh C,
Dean William L,
Roberts Andrew M
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a488-d
Subject(s) - mapk/erk pathway , chemistry , kinase , protein kinase a , extracellular , microbiology and biotechnology , biophysics , bovine serum albumin , permeability (electromagnetism) , biochemistry , biology , membrane
Fibrinogen (Fg)‐induced endothelial cell (EC) permeability was studied using rat cardiac microvascular ECs grown in Transwells or chambered cover glass plates. Confluent ECs were given one of the following treatments: Fg (2 or 4 mg/ml), Fg (4 mg/ml) with extracellular signal‐regulated kinase (ERK) kinase inhibitors (PD98059, or U0126), Fg (4 mg/ml) with antibodies against intercellular adhesion molecule‐1 (ICAM‐1) or α 5 β 1 integrin, or medium (control) for 30 min. EC permeability to bovine serum albumin conjugated with a fluorescent dye was assessed by measuring fluorescence intensity (FIU) of the solutes in the Transwells' lower chambers. Formation of filamentous actin (F‐actin) and ERK phosphorylation were assessed by confocal microscopy. Fg caused a dose‐dependent increase in EC permeability (150 ±11 and 337 ± 28 FIU for 2 and 4 mg/ml Fg respectively, vs. 52 ± 5 FIU for control, mean±SE). Fg‐induced EC permeability was inhibited by ERK kinase inhibitors or by the antibodies to ICAM‐1 and α 5 β 1 . Fg dose‐dependently increased F‐actin formation and its associated gap formation between cells. These changes were inhibited by the ERK kinase inhibitors or by the antibodies to ICAM‐1 and α 5 β 1 . Fg‐induced ERK phosphorylation was inhibited by the ERK kinase inhibitors. These data suggest that Fg may increase EC permeability through ERK signaling which leads to formation of F‐actin that enhances gap formation between ECs.