A fibrin biofilm covers blood clots and protects from microbial invasion
Fraser L. Macrae, … , Heiko Herwald, Robert A.S. Ariëns
Fraser L. Macrae, … , Heiko Herwald, Robert A.S. Ariëns
Published May 3, 2018
Citation Information: J Clin Invest. 2018;128(8):3356-3368. https://doi.org/10.1172/JCI98734.
View: Text | PDF
Research Article Hematology Vascular biology

A fibrin biofilm covers blood clots and protects from microbial invasion

Abstract

Hemostasis requires conversion of fibrinogen to fibrin fibers that generate a characteristic network, interact with blood cells, and initiate tissue repair. The fibrin network is porous and highly permeable, but the spatial arrangement of the external clot face is unknown. Here we show that fibrin transitioned to the blood-air interface through Langmuir film formation, producing a protective film confining clots in human and mouse models. We demonstrated that only fibrin is required for formation of the film, and that it occurred in vitro and in vivo. The fibrin film connected to the underlying clot network through tethering fibers. It was digested by plasmin, and formation of the film was prevented with surfactants. Functionally, the film retained blood cells and protected against penetration by bacterial pathogens in a murine model of dermal infection. Our data show a remarkable aspect of blood clotting in which fibrin forms a protective film covering the external surface of the clot, defending the organism against microbial invasion.

Authors

Fraser L. Macrae, Cédric Duval, Praveen Papareddy, Stephen R. Baker, Nadira Yuldasheva, Katherine J. Kearney, Helen R. McPherson, Nathan Asquith, Joke Konings, Alessandro Casini, Jay L. Degen, Simon D. Connell, Helen Philippou, Alisa S. Wolberg, Heiko Herwald, Robert A.S. Ariëns

×

Figure 6

Fibrin film formation in vivo.

Options: View larger image (or click on image) Download as PowerPoint
Fibrin film formation in vivo. (A) Clots were formed in a ventral, derma...
(A) Clots were formed in a ventral, dermal puncture injury model in mice and left clear or covered with a layer of mineral oil, fixed, dehydrated, and imaged by SEM. The white box represents the area of magnification for the image to the right. Clots covered with oil showed a rough fibrous clot surface, and clots left untreated showed a smooth fibrin film covering the clot. Images are representative of n = 4 mice. Scale bars: left, 1 mm; right, 2 μm. (B) Clots left clear or with a layer of oil covering the surface from the dermal puncture model were surgically removed, and cross sections were stained with MSB (erythrocytes in yellow, fibrin in pink). Fibrin film shows as continuous pink layer; clot appears yellow interspersed with pink. Asterisks highlight the air-liquid interface. Images are representative of n = 4 mice. (C) Clots from the murine dermal puncture model covered with oil showed extrusion of red blood cells from the clot in the absence of a fibrin film. Asterisk highlights extrusion of red blood cells from the clot. Image is representative of n = 4 mice. (D) Clots produced with human whole blood and thrombin and imaged by SEM demonstrated containment red blood cells by the fibrin film. Image is representative of n = 3 individuals. Scale bar: 40 μm. (E) Hemoglobin retention assay in normal, perforated, and Tween-20–treated clots. ***P < 0.001 compared with normal clot; n = 3 individuals; 1-way ANOVA, F = 52.14, df = 2, P = 0.0002. Hb, hemoglobin.