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.
Highlights
AMPs are usually derived from larger precursors that contain signal peptides
It shows that respiratory epithelial cells (REC) gave a more intense response to IL-1βthan pathogen-associated molecular patterns (PAMPs) (Fig. 1a)
B2M, a low molecular mass protein (Mr of 11729), is found as a free form in the serum and as a form noncovalently associated with the alpha chain of class I major histocompatibility complex (MHC) molecule on the cell surface[33]
Summary
AMPs are usually derived from larger precursors that contain signal peptides. Some other AMPs are produced from larger proteins cleaved by proteolysis, such as buforin II19, lactoferricin[20] and LL-3721. With respect to the negative charge conserved on the membrane surface of pathogens, almost all AMPs consist of cationic and hydrophobic domains at physiological pH22. Based on this feature, cleavage and release (shedding) of www.nature.com/scientificreports/. Peptides that are up-regulated after stimulation are highlighted (*) and their masses are indicated. This spectrum represents one of three analyzed samples. Chemokines orchestrate a wide range of physiological and pathological processes, including immune surveillance[25], modulation of effector cell function within tissue[26], inflammation[27], tumorigenesis and cancer metastasis[28].
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