Studies on Polymorphonuclear Leukocyte Bactericidal Function III: The Role of Extracellular Matrix Proteins

Abstract

We investigated the effect of the extracellular matrix proteins fibronectin (Fn) and laminin (Ln) on polymorphonuclear leukocytes (PMN) bactericidal activity. Adherence of PMN to increasing concentrations of Ln significantly increased the killing ofEscherichia coliafter 240 min of adherence, while fibronectin significantly increased PMN staphlacidal activity after 240 min of adherence. The addition of IL-1β and IL-8 but not TNF-α increased PMN bactericidal activity againstE. coliwhen PMN were adhered to Ln, while TNF-α and IL-8 increased PMN bactericidal activity againstStaphylococcus aureuswhen PMN were adhered to Ln. TNF-α increased PMN killing ofE. coliwhen PMN were adhered to Fn, while only IL-1β increased the killing ofS. aureuswhen PMN were adhered to FN. Anti-VLA-3 (α3/β1) monoclonal antibodies (mAbs) inhibited the effect of Ln on PMN bactericidal activity, while anti-VLA-5 (α5/β1) mAbs inhibited the effect of Fn on PMN bactericidal activity. Progressive cross-linkage of these two receptors led to a dose-dependent reduction in PMN bactericidal activity for both pathogens when PMN were adhered to Ln or Fn, respectively. These results demonstrate that extracellular matrix proteins ± exogenously added cytokines have the capacity to regulate PMN bactericidal activity. The signals sent by these matrix proteins to increase PMN bactericidal activity are transduced primarily via separate α subunits of the β1 integrin complex. Stimulation of these receptors might lead to potential upregulation of PMN bactericidal activity which would be potentially advantageousin vivoat sites of infection.