The Coagulation and Immune Systems Are Directly Linked Through the Activation of Interleukin-1α by Thrombin

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2019 Mar 31

PMID 30926232

Citations 95

Authors

Laura C Burzynski

Melanie Humphry

Katerina Pyrillou

Kimberley A Wiggins

Julie N E Chan

Nichola Figg

Lauren L Kitt

Charlotte Summers

Kate C Tatham

Paul B Martin

Martin R Bennett

Murray C H Clarke

Affiliations

Soon will be listed here.

Abstract

Ancient organisms have a combined coagulation and immune system, and although links between inflammation and hemostasis exist in mammals, they are indirect and slower to act. Here we investigated direct links between mammalian immune and coagulation systems by examining cytokine proproteins for potential thrombin protease consensus sites. We found that interleukin (IL)-1α is directly activated by thrombin. Thrombin cleaved pro-IL-1α at a site perfectly conserved across disparate species, indicating functional importance. Surface pro-IL-1α on macrophages and activated platelets was cleaved and activated by thrombin, while tissue factor, a potent thrombin activator, colocalized with pro-IL-1α in the epidermis. Mice bearing a mutation in the IL-1α thrombin cleavage site (R114Q) exhibited defects in efficient wound healing and rapid thrombopoiesis after acute platelet loss. Thrombin-cleaved IL-1α was detected in humans during sepsis, pointing to the relevance of this pathway for normal physiology and the pathogenesis of inflammatory and thrombotic diseases.

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