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Blood. 2019 Jul 18;134(3):291-303. doi: 10.1182/blood.2018874859. Epub 2019 May 17.

Plasmin-mediated fibrinolysis enables macrophage migration in a murine model of inflammation.

Author information

1
Proteases and Tissue Remodeling Section and.
2
Oral Inflammation and Immunity Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD.
3
Division of Hematology and.
4
Division of Experimental Hematology, Cancer and Blood Diseases Institute, Cincinnati Children's Research Foundation, Cincinnati, OH; and.
5
College of Medicine, University of Cincinnati, Cincinnati, OH.

Abstract

Efficient migration of macrophages to sites of inflammation requires cell surface-bound plasmin(ogen). Here, we investigated the mechanisms underlying the deficits of plasmin(ogen)-mediated macrophage migration in 2 models: murine thioglycollate-induced peritonitis and in vitro macrophage migration. As previously reported, macrophage migration into the peritoneal cavity of mice in response to thioglycollate was significantly impaired in the absence of plasminogen. Fibrin(ogen) deposition was noted in the peritoneal cavity in response to thioglycollate, with a significant increase in fibrin(ogen) in the plasminogen-deficient mice. Interestingly, macrophage migration was restored in plasminogen-deficient mice by simultaneous imposition of fibrinogen deficiency. Consistent with this in vivo finding, chemotactic migration of cultured macrophages through a fibrin matrix did not occur in the absence of plasminogen. The macrophage requirement for plasmin-mediated fibrinolysis, both in vivo and in vitro, was negated by deletion of the major myeloid integrin αMβ2-binding motif on the γ chain of fibrin(ogen). The study identifies a critical role of fibrinolysis in macrophage migration, presumably through the alleviation of migratory constraints imposed by the interaction of leukocytes with fibrin(ogen) through the integrin αMβ2 receptor.

PMID:
31101623
DOI:
10.1182/blood.2018874859

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