Staphylococcal induced inflammatory response in human monocytes: Analysis of factors involved

Sammanfattning: Purified bacterial cell wall components peptidoglycan and teichoic acid were isolated from staphylococcal species S. aureus and/or S. epidermidis and tested for their ability to induce cytokine release from plastic-adherent human monocytes. Both cell wall components dose-dependently induced TNF-alpha, interleukin-1beta, and interleukin-6 release, peptidoglycan being more potent than teichoic acid. Reducing the molecular size of peptidoglycan with enzymes or sonication resulted in a loss of TNF-alpha-inducing capacity. Human serum highly potentiated peptidoglycan-induced TNF-alpha release, as measured by ELISA and bioassay. Using deficient and depleted sera it was shown that complement components and immunoglobulin G were involved. The differential effects of intracellular pathway inhibitors on TNF-alpha release were studied using monocytes stimulated by peptidoglycan from S. epidermidis or lipopolysaccharide (LPS) from Escherichia coli in the presence of 10% human serum. The results showed an involvement of calmodulin-dependent protein kinase, protein tyrosine kinase, and a cholera-toxin-sensitive G protein in peptidoglycan- and LPS-induced TNF-alpha release. A S. epidermidis isolate was incubated with 5x minimum inhibitory concentrations of penicillin, oxacillin, vancomycin, or clindamycin. Supernatants from the cultures were tested for TNF-alpha release in the absence or presence of serum. Beta-lactam antibiotics generated significantly more TNF-alpha-releasing material than vancomycin, clindamycin or the bacteria as such. Soluble peptidoglycan and teichoic acid contents estimated by inhibition ELISA correlated with TNF-alpha release.