Post-traumatic osteomyelitis: analysis of inflammatory cells recruited into the site of infection.

Device-associated infections after implants or endoprostheses inflict local inflammation and ultimately osteolysis, a clinical entity referred to as posttraumatic osteomyelitis. The underlying molecular mechanisms are not yet known; formation of bacterial biofilms on the implant is presumed, conferring resistance to antibiotics and to host defense mechanisms as well. To gain insight into the pathogenesis of post-traumatic osteomyelitis, the infected site was analyzed for the presence of immunocompetent cells. In 18 patients, the infected site was rinsed intraoperatively. This so-called lavage contained 1-2 x 107 leukocytes, predominantly highly activated polymorphonuclear neutrophils (PMNs), as characterized by low expression of CD62L (selectin), and high expression of the adhesion protein CD18, of the high-affinity immunoglobulin (IgG) receptor CD64, and of the LPS-receptor CD14. CD16, the low-affinity IgG receptor, was affected in some patients only. Because the majority of infections were caused by staphylococci species, the effect of bacteria-derived lipoteichoic acid on PMN of healthy donors was tested in vitro. A similar activation pattern was found: rapid down-regulation of CD62L, a slower loss of CD16, and upregulation of CD18, CD64, and CD14. Lipoteichoic acid signaling required p38 mitogen-activated protein kinase and resulted in induction of CD14-specific mRNA and de novo protein synthesis. We conclude that PMNs infiltrate the infected site, but despite local activation they are unable to clear the bacteria, presumably because of biofilm formation. Our data are consistent with the hypothesis that during the ineffective "frustrated" attempt to phagocytose, PMNs release cytotoxic and proteolytic entities that in turn contribute to the progression of tissue injury and ultimately to osteolysis.