Induction and antimicrobial activity of platelet basic protein derivatives in human monocytes.
The antimicrobial activity of a number of chemokines has recently come into focus of research about innate immunity. We have previously shown that platelet basic protein (PBP), which gives rise to several antimicrobial peptides of platelets, is also expressed in human monocytes. In the present studies, we show that exposure of human monocytes to bacteria or microbial components (lipopolysaccharide and zymosan) induces a several-fold greater expression of derivates of PBP. Also, activation of proteinase-activated receptors (PARs) by thrombin or the synthetic peptide ligand SFLLRN of PAR-1 significantly increased PBP expression, presumably on the transcriptional level, as evidenced by higher mRNA levels. Derivates of PBP appeared to reach phago-lysosomes, as higher concentration was found in latex phagosomes isolated by a flotation method. By the gel-overlay technique, two bactericidal derivatives of PBP could be visualized, which were immunoreactive with anti-PBP antibody in Western blots. By matrix-assisted laser desorption/ionization time of flight and surface-enhanced laser desorption and ionization techniques, it was confirmed that the bands corresponded to PBP derivates. After immunofixation with a monoclonal antibody to PBP, the major peptide in zymosan-stimulated monocytes was identified to correspond by molecular weight to connective tissue-activating peptide III, which has been reported to be a major antimicrobial PBP derivate also in platelets. Our observations indicate that PBP and its derivates are constituents of the antimicrobial arsenal of human monocytes. Their increased expression after exposure to microorganisms allows a rapid host response to pathogens.
Division of Infectious Diseases, University of California San Diego, USA. klinsar@usz.unizh.ch
Andreas
A
Schaffner
Charles C
CC
King
Dominik
D
Schaer
Donald G
DG
Guiney
D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D001424:Bacterial Infections / Q000276:immunology*; D002460:Cell Line; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D044462:Receptors, Proteinase-Activated / Q000187:drug effects / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D015054:Zymosan / Q000494:pharmacology; D001620:beta-Thromboglobulin
D023181:Antimicrobial Cationic Peptides; D018925:Chemokines; D008070:Lipopolysaccharides; C061615:PPBP protein, human; D010446:Peptide Fragments; D010455:Peptides; D012333:RNA, Messenger; D044462:Receptors, Proteinase-Activated; D001620:beta-Thromboglobulin; C082835:thrombin receptor peptide (42-47); C009862:connective tissue-activating peptide; D015054:Zymosan; D013917:Thrombin