Peptidoglycan recognition protein-peptidoglycan complexes increase monocyte/macrophage activation and enhance the inflammatory response.
Peptidoglycan recognition proteins (PGRP) are pattern recognition receptors that can bind or hydrolyse peptidoglycan (PGN). Four human PGRP have been described: PGRP-S, PGRP-L, PGRP-Iα and PGRP-Iβ. Mammalian PGRP-S has been implicated in intracellular destruction of bacteria by polymorphonuclear cells, PGRP-Iα and PGRP-Iβ have been found in keratinocytes and epithelial cells, and PGRP-L is a serum protein that hydrolyses PGN. We have expressed recombinant human PGRP and observed that PGRP-S and PGRP-Iα exist as monomer and disulphide dimer proteins. The PGRP dimers maintain their biological functions. We detected the PGRP-S dimer in human serum and polymorphonuclear cells, from where it is secreted after degranulation; these cells being a possible source of serum PGRP-S. Recombinant PGRP do not act as bactericidal or bacteriostatic agents in the assayed conditions; however, PGRP-S and PGRP-Iα cause slight damage in the bacterial membrane. Monocytes/macrophages increase Staphylococcus aureus phagocytosis in the presence of PGRP-S, PGRP-Iα and PGRP-Iβ. All PGRP bind to monocyte/macrophage membranes and are endocytosed by them. In addition, all PGRP protect cells from PGN-induced apoptosis. PGRP increase THP-1 cell proliferation and enhance activation by PGN. PGRP-S-PGN complexes increase the membrane expression of CD14, CD80 and CD86, and enhance secretion of interleukin-8, interleukin-12 and tumour necrosis factor-α, but reduce interleukin-10, clearly inducing an inflammatory profile.
Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-UBA, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.|Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Buenos Aires, Argentina.|Instituto de Ecología y Desarrollo Sustentable (INEDES), Luján, Buenos Aires, Argentina.
Mauricio C
MC
De Marzi
Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-UBA, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.|Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Buenos Aires, Argentina.|Instituto de Ecología y Desarrollo Sustentable (INEDES), Luján, Buenos Aires, Argentina.
Marcos
M
Todone
Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-UBA, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
María B
MB
Ganem
W. M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, USA.
Qian
Q
Wang
W. M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, USA.
Roy A
RA
Mariuzza
Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-UBA, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Marisa M
MM
Fernández
Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-UBA, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Emilio L
EL
Malchiodi
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001419:Bacteria / Q000187:drug effects / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010457:Peptidoglycan / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D011485:Protein Binding / Q000276:immunology
D002352:Carrier Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D010457:Peptidoglycan; C118897:peptidoglycan recognition protein
Staphylococcus aureus; innate immunity; monocyte; peptidoglycan; peptidoglycan recognition protein