Alpha-2-Macroglobulin in Inflammation, Immunity and Infections

Front Immunol. 2021 Dec 14;12:803244. doi: 10.3389/fimmu.2021.803244. eCollection 2021.

Abstract

Alpha-2-macroglobulin is an extracellular macromolecule mainly known for its role as a broad-spectrum protease inhibitor. By presenting itself as an optimal substrate for endopeptidases of all catalytic types, alpha-2-macroglobulin lures active proteases into its molecular cage and subsequently 'flags' their complex for elimination. In addition to its role as a regulator of extracellular proteolysis, alpha-2-macroglobulin also has other functions such as switching proteolysis towards small substrates, facilitating cell migration and the binding of cytokines, growth factors and damaged extracellular proteins. These functions appear particularly important in the context of immune-cell function. In this review manuscript, we provide an overview of all functions of alpha-2-macroglobulin and place these in the context of inflammation, immunity and infections.

Keywords: alpha-2-macroglobulin; immunity; infections; inflammation; macrophages; neutrophils; proteolysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Communicable Diseases / diagnosis
  • Communicable Diseases / etiology*
  • Communicable Diseases / metabolism*
  • Complement Activation / genetics
  • Complement Activation / immunology
  • Complement System Proteins / immunology
  • Cytokines / metabolism
  • Diagnosis, Differential
  • Disease Susceptibility*
  • Endopeptidases
  • Humans
  • Immunity*
  • Inflammation / diagnosis
  • Inflammation / etiology*
  • Inflammation / metabolism*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Leukocytes / pathology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Pregnancy-Associated alpha 2-Macroglobulins / genetics*
  • Pregnancy-Associated alpha 2-Macroglobulins / metabolism*
  • Protein Binding
  • Proteolysis
  • Signal Transduction

Substances

  • Biomarkers
  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • Pregnancy-Associated alpha 2-Macroglobulins
  • Complement System Proteins
  • Endopeptidases