Stimulation of human neutrophils and monocytes by staphylococcal phenol-soluble modulin

Modulins represent microbial products that stimulate cytokine production in host cells. The modulins responsible for gram-positive sepsis remain poorl y understood, Staphylococci release a factor (or factors) that activates nu clear factor-kappaB and stimulates cytokine production in cells of macropha ge lineage, This factor, termed phenol-soluble modulin (PSM), has been rece ntly isolated from culture supernatant of Staphylococcus epidermidis, We ex amined the effects of PSM on proinflammatory properties of human neutrophil s and monocytes in vitro. PSM activated the respiratory (oxidative) burst i n neutrophils and primed neutrophils for enhanced respiratory burst activit y in response to formyl-methionyl-leucyl-phenylalanine. PSM also stimulated neutrophil degranulation as reflected by increased surface expression of C D11b and CD18, which was accompanied by rapid shedding of L-selectin. Spont aneous apoptosis Of both neutrophils and monocytes was inhibited by PSM, Fu rthermore, PSM also functioned as a chemoattractant factor for both neutrop hils and monocytes, Thus, the proinflammatory properties of PSM resemble th ose of both lipopolysaccharide and bacterial chemotactic peptides, These fi ndings suggest that PSM may play a role in the pathogenesis and systemic ma nifestations of sepsis caused by staphylococci.