Cytokine-induced respiratory burst of human neutrophils: dependence on extracellular matrix proteins and CD11/CD18 integrins.
Human polymorphonuclear leukocytes (PMN) released large quantities of hydrogen peroxide in response to tumor necrosis factor, but only when the cells were adherent to surfaces coated with extracellular matrix proteins. The PMN did not respond when exposed to cytokines and matrix proteins in suspension, or when exposed to cytokines while adherent to surfaces coated with stearic acid. PMN from children with genetic deficiency of the CD11/CD18 integrins underwent a normal respiratory burst upon adherence to uncoated polystyrene, but not in response to tumor necrosis factor when tested on polystyrene that was coated with serum, fibronectin, vitronectin, fibrinogen, thrombospondin, or laminin. Anti-CD18 antibodies, alone of sixteen antibodies tested, induced a similar defect in PMN from normal donors, when the PMN were tested on surfaces coated with serum, fibrinogen, thrombospondin, or laminin; no defect was induced by the anti-CD18 monoclonal antibody IB4 in normal PMN tested on surfaces coated with fibronectin or vitronectin. Thus, for cytokines to induce a respiratory burst in PMN, the cells must be able to use CD11/CD18 integrins and must interact with matrix proteins in the solid phase. CD11/CD18, which is already known to serve as a receptor for fibrinogen, may also be a receptor for thrombospondin and laminin. Finally, receptor(s) exist on PMN for fibronectin and vitronectin which are not blocked by the anti-CD18 antibody IB4 but which are nonetheless CD11/CD18 dependent.
Nathan
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C
Department of Medicine, Cornell University Medical College, New York 10021.
Srimal
S
S
Farber
C
C
Sanchez
E
E
Kabbash
L
L
Asch
A
A
Gailit
J
J
Wright
S D
SD
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000276:immunology; D001685:Biological Factors / Q000494:pharmacology*; D002448:Cell Adhesion; D002648:Child; D016207:Cytokines; D005109:Extracellular Matrix / Q000502:physiology*; D005340:Fibrinogen / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood*; D066298:In Vitro Techniques; D007700:Kinetics; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019699:Thrombospondins; D019096:Vitronectin
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D001685:Biological Factors; D016207:Cytokines; D005353:Fibronectins; D006023:Glycoproteins; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D019699:Thrombospondins; D019096:Vitronectin; D005340:Fibrinogen; D006861:Hydrogen Peroxide; D013755:Tetradecanoylphorbol Acetate