Neutrophil bactericidal activity against Staphylococcus aureus adherent on biological surfaces. Surface-bound extracellular matrix proteins activate intracellular killing by oxygen-dependent and -independent mechanisms.
The activation patterns of surface adherent neutrophils are modulated via interaction of extracellular matrix proteins with neutrophil integrins. To evaluate neutrophil bactericidal activity, Staphylococcus aureus adherent to biological surfaces were incubated with neutrophils and serum, and the survival of surface bacteria was determined. When compared to albumin-coated surfaces, the bactericidal activity of neutrophils adherent to purified human extracellular matrix was markedly enhanced (mean survival: 34.2% +/- 9.0% of albumin, P less than 0.0001) despite similar efficient ingestion of extracellular bacteria. Enhancement of killing was observed when surfaces were coated with purified constituents of extracellular matrix, i.e., fibronectin, fibrinogen, laminin, vitronectin, or type IV collagen. In addition to matrix proteins, the tetrapeptide RGDS (the sequence recognized by integrins) crosslinked to surface bound albumin was also active (survival: 74.5% +/- 5.5% of albumin, P less than 0.02), and fibronectin-increased killing was inhibited by soluble RGDS. Chemiluminescence measurements and experiments with CGD neutrophils revealed that both oxygen-dependent and -independent bactericidal mechanisms are involved. In conclusion, matrix proteins enhance intracellular bactericidal activity of adherent neutrophils, presumably by integrin recognition of RGDS-containing ligands. These results indicate a role for extracellular matrix proteins in the enhancement of the host defense against pyogenic infections.
Division of Infectious Diseases, University Hospital, Geneva, Switzerland.
M
M
Hermann
M E
ME
Jaconi
C
C
Dahlgren
F A
FA
Waldvogel
O
O
Stendahl
D P
DP
Lew
D000595:Amino Acid Sequence; D001770:Blood Bactericidal Activity; D002448:Cell Adhesion; D005109:Extracellular Matrix / Q000502:physiology*; D005340:Fibrinogen / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D006105:Granulomatous Disease, Chronic / Q000503:physiopathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D016023:Integrins / Q000502:physiology; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology*; D009842:Oligopeptides; D010100:Oxygen / Q000633:toxicity; D010587:Phagocytosis; D013211:Staphylococcus aureus / Q000276:immunology; D013329:Structure-Activity Relationship
D005353:Fibronectins; D016023:Integrins; D009842:Oligopeptides; D005340:Fibrinogen; D006861:Hydrogen Peroxide; D010100:Oxygen