info:eu-repo/semantics/article
Peptidoglycan recognition protein–peptidoglycan complexes increase monocyte/macrophage activation and enhance the inflammatory response
Fecha
2015-03Registro en:
de Marzi, Mauricio Cesar; Todone, Marcos; Ganem, María Bernarda; Wang, Qian; Mariuzza, Roy A.; et al.; Peptidoglycan recognition protein–peptidoglycan complexes increase monocyte/macrophage activation and enhance the inflammatory response; Wiley; Immunology; 145; 3; 3-2015; 429-442
0019-2805
Autor
de Marzi, Mauricio Cesar
Todone, Marcos
Ganem, María Bernarda
Wang, Qian
Mariuzza, Roy A.
Fernández, Marisa Mariel
Malchiodi, Emilio Luis
Resumen
Peptidoglycan recognition proteins (PGRPs) are pattern recognition receptors (PRRs) that can bind or hydrolyze peptidoglycan (PGN). Humans have 4 PGRPs denominated PGRP-S, PGRP-L, PGRP-Iα and PGRP-Iβ. Mammalian PGRP-S has been implicated in intracellular destruction of bacteria by polymorphonuclear cells (PMN), PRGP-Iα and PGRP-Iβ have been found in keratinocytes and epithelial cells while PGRP-L is a serum protein that hydrolyzes PGNs. We expressed here recombinant human PGRPs and observed that PGRP-S and PGRP-Iα exist as monomer and disulfide dimer proteins. PGRPs dimers maintain their biological functions. We detected PGRP-S dimer in human serum and PMN, from where it is secreted after degranulation, being these cells a possible source of serum PGRP-S. Recombinant PGRPs 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 S. aureus phagocytosis in the presence of PGRP-S, PGRP-Iα and PGRP-Iβ. All PGRPs bind to monocyte/macrophage membrane and are endocyted by them. In addition, all PGRPs protect cells from PGN-induced apoptosis. PGRPs 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 IL-8, IL-12and TNF-α, but reduce IL-10, clearly inducing an inflammatory profile