An in vitro model of the wound microenvironment: local phagocytic cell abnormalities associated with in situ complement activation.
An in vitro model was developed to investigate the inflammatory response to tissue damage. Human fibroblasts were heat killed and incubated with serum. Complement studies showed activation of the alternative pathway proportional to the number of dead cells; C3 was fixed on dead cells, and C5a was generated. Neutrophils (PMNLs) adhered to killed fibroblasts, a process requiring fresh serum. After adhering to killed fibroblasts in the presence of serum, PMNLs exhibited depressed chemotactic responsiveness to activated serum and reduced bactericidal activity against preopsonized Staphylococcus aureus. These data suggest that thermally killed cells activate and fix complement, a process generating cleavage products that, in turn, recruit PMNLs and bind them to the inflammatory site. Thus, in our model, dead tissue activates humoral mechanisms and inflammatory cells; this process results in depressed in situ host-defense function upon subsequent local challenge with microbes.
D001770:Blood Bactericidal Activity; D002448:Cell Adhesion; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D003167:Complement Activation; D003170:Complement Pathway, Alternative; D005347:Fibroblasts / Q000276:immunology*; D006801:Humans; D008297:Male; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis; D013211:Staphylococcus aureus / Q000276:immunology; D013481:Superoxides / Q000378:metabolism; D014947:Wounds and Injuries / Q000276:immunology*
D013481:Superoxides; D009113:Muramidase