Mammalian PGRPs: novel antibacterial proteins.
Peptidoglycan recognition proteins (PGRPs) are innate immunity molecules conserved from insects to mammals. Insects have up to 19 PGRPs, which activate Toll or Imd signal transduction pathways or induce proteolytic cascades that generate antimicrobial products, induce phagocytosis, hydrolyse peptidoglycan, and protect insects against infections. Mammals have four PGRPs, which were hypothesized to function as signal-transducing pattern recognition receptors. However, all mammalian PGRPs are secreted, usually as disulphide-linked homo- and heterodimers. One mammalian PGRP, PGLYRP-2, is an N-acetylmuramoyl-L-alanine amidase that hydrolyses bacterial peptidoglycan and reduces its proinflammatory activity. PGLYRP-2 is secreted from liver into blood, and is also induced by bacteria in epithelial cells. The three remaining mammalian PGRPs are bactericidal or bacteriostatic proteins. PGLYRP-1 is expressed primarily in the granules of polymorphonuclear leucocytes (PMNs) , and PGLYRP-3 and PGLYRP-4 are expressed in the skin, eyes, salivary glands, throat, tongue, esophagus, stomach and intestine, and protect the host against infections. They kill bacteria by interacting with their cell wall peptidoglycan, rather than permeabilizing their membranes. These PGRPs therefore are a new class of bactericidal and bacteriostatic proteins that have different structure, mechanism of action, and expression pattern from currently known vertebrate antimicrobial peptides. Direct bactericidal activity of these PGRPs either evolved in vertebrates or mammals, or it is yet to be discovered in insects.
Dziarski
Roman
R
Indiana University School of Medicine-Northwest, Gary, IN 46408, USA. rdziar@iun.edu
Gupta
Dipika
D
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D019476:Insect Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D008322:Mammals / Q000276:immunology / Q000378:metabolism*; D008958:Models, Molecular; D010457:Peptidoglycan / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D019476:Insect Proteins; D010457:Peptidoglycan; C118897:peptidoglycan recognition protein