Abstract
We analyzed a panel of cationic molecules secreted in the culture medium of human respiratory epithelial cells (REC) upon activation by IL-1β and different pathogen-associated molecular patterns. A 9 kDa fragment derived from β2-microglobulin (B2M) was identified and named shed 9 kDa B2M (sB2M-9). The primary structure of sB2M-9 was revealed to increase its pI value that potentially could play an important role in innate defense. sB2M-9 exhibits antibacterial activity against Gram positive Staphylococcus aureus (SA) but not against Gram negative Klebsiella pneumonia (KP). Upon its binding to SA, sB2M-9 induces clumps, a phenomenon not observed with B2M. Migration of THP-1 monocytes exposed to SA clumps was significantly greater than that to SA without clumps. sB2M-9 binds to SA, more likely as a chemokine, to facilitate THP-1 migration. As a whole, we demonstrated that REC release a novel chemokine with antibacterial activity that is shed from B2M to facilitate THP-1 migration.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Sequence
-
Anti-Bacterial Agents / immunology*
-
Antimicrobial Cationic Peptides / immunology*
-
Cell Line
-
Chemokine CXCL5 / immunology
-
Chemokines / immunology*
-
Humans
-
Immunity, Innate
-
Interleukin-1beta / immunology
-
Monocytes / immunology
-
Nuclear Proteins / immunology
-
Pathogen-Associated Molecular Pattern Molecules / immunology
-
Peptide Fragments / chemistry
-
Peptide Fragments / genetics
-
Peptide Fragments / immunology
-
Respiratory Mucosa / immunology*
-
Respiratory Mucosa / microbiology
-
Staphylococcus aureus / immunology
-
Staphylococcus aureus / pathogenicity
-
Suppressor of Cytokine Signaling Proteins / immunology
-
THP-1 Cells
-
beta 2-Microglobulin / chemistry
-
beta 2-Microglobulin / genetics
-
beta 2-Microglobulin / immunology*
Substances
-
Anti-Bacterial Agents
-
Antimicrobial Cationic Peptides
-
CXCL5 protein, human
-
Chemokine CXCL5
-
Chemokines
-
Interleukin-1beta
-
Nuclear Proteins
-
Pathogen-Associated Molecular Pattern Molecules
-
Peptide Fragments
-
SOCS7 protein, human
-
Suppressor of Cytokine Signaling Proteins
-
beta 2-Microglobulin