Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond

Guacyara Motta; Luiz Juliano; Jair Ribeiro Chagas

doi:10.3389/fphys.2023.1188816

Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond

Front Physiol. 2023 Aug 30:14:1188816. doi: 10.3389/fphys.2023.1188816. eCollection 2023.

Authors

Guacyara Motta¹, Luiz Juliano², Jair Ribeiro Chagas²

Affiliations

¹ Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
² Departamento de Biofisica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.

Abstract

Human plasma kallikrein (PKa) is obtained by activating its precursor, prekallikrein (PK), historically named the Fletcher factor. Human PKa and tissue kallikreins are serine proteases from the same family, having high- and low-molecular weight kininogens (HKs and LKs) as substrates, releasing bradykinin (Bk) and Lys-bradykinin (Lys-Bk), respectively. This review presents a brief history of human PKa with details and recent observations of its evolution among the vertebrate coagulation proteins, including the relations with Factor XI. We explored the role of Factor XII in activating the plasma kallikrein-kinin system (KKS), the mechanism of activity and control in the KKS, and the function of HK on contact activation proteins on cell membranes. The role of human PKa in cell biology regarding the contact system and KSS, particularly the endothelial cells, and neutrophils, in inflammatory processes and infectious diseases, was also approached. We examined the natural plasma protein inhibitors, including a detailed survey of human PKa inhibitors' development and their potential market.

Keywords: bradykinin; cell biology; inflammation; inhibitors; kallikrein; kininogen; proteolysis.

Publication types

Review

Grants and funding

This work received financial support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES-Brasil; Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq – 313324/2022-0)-Brasil and Fundação de Amparo à Pesquisa do Estado de São Paulo-Brasil (FAPESP- 2020/07065-4).