What question did this study set out to answer?

To define the in vivo physiological significance of leukocyte integrin alpha(M)beta(2)/Mac-1 binding to fibrinogen during host inflammatory responses.

June 1, 2004Journal of Clinical InvestigationOpen Access

Leukocyte engagement of fibrin(ogen) via the integrin receptor αMβ2/Mac-1 is critical for host inflammatory response in vivo

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To define the in vivo physiological significance of leukocyte integrin alpha(M)beta(2)/Mac-1 binding to fibrinogen during host inflammatory responses.
Generated gene-targeted mice harboring alanine substitutions in the alpha(M)beta(2)-binding motif of the fibrinogen gamma chain (Fibgamma[390-396A]).
Evaluated systemic clotting, platelet aggregation, and in vitro leukocyte adhesion using primary neutrophils, macrophages, and Mac-1-expressing cell lines.
Inoculated mutant and wild-type mice intraperitoneally with Staphylococcus aureus to evaluate leukocyte trafficking and antimicrobial clearance in vivo.
Fibgamma(390-396A) mice displayed normal fibrinogen levels, normal clotting function, intact platelet aggregation, and no spontaneous bleeding.
Mutant fibrinogen completely failed to mediate alpha(M)beta(2)-dependent adhesion of primary neutrophils and macrophages.
Disruption of the alpha(M)beta(2)-binding motif caused a severe defect in peritoneal clearance of Staphylococcus aureus due to impaired leukocyte antimicrobial activation rather than reduced cell recruitment.

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Implication

Gene-targeted mouse study demonstrates impaired bacterial clearance after disrupting fibrinogen-integrin binding, indicating that fibrinogen drives leukocyte antimicrobial activity independently...

Cite This Study

Flick et al. (2004) studied this question.

synapsesocial.com/papers/6a6f93006c240de38cdb8594 https://doi.org/10.1172/jci20741

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Implication

Gene-targeted mouse study demonstrates impaired bacterial clearance after disrupting fibrinogen-integrin binding, indicating that fibrinogen drives leukocyte antimicrobial activity independently...

Leukocyte engagement of fibrin(ogen) via the integrin receptor αMβ2/Mac-1 is critical for host inflammatory response in vivo

Key Points

Discussion

Implication

Cite This Study

Leukocyte engagement of fibrin(ogen) via the integrin receptor αMβ2/Mac-1 is critical for host inflammatory response in vivo

Key Points

Discussion

Implication

Cite This Study

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