Leukocyte response integrin and integrin-associated protein act as a signal transduction unit in generation of a phagocyte respiratory burst.
The leukocyte response integrin (LRI) is a phagocyte integrin which recognizes the basement membrane protein entactin and the synthetic peptide Lys-Gly-Ala-Gly-Asp-Val (KGAGDV). The function of LRI is intimately associated with that of a distinct membrane protein, integrin-associated protein (IAP), as antibodies which recognizes IAP can inhibit all known functions of LRI. When adherent to surface, the LRI ligands entactin and KGAGDV activate the respiratory burst in polymorphonuclear leukocytes (PMN) and monocytes, as do monoclonal antibodies (mAb) directed at either LRI or IAP. When added in solution, peptides and antibodies specific for LRI, and some, but not all, anti-IAP antibodies, can inhibit the respiratory burst activated by any of these surface-adherent ligands. Only monoclonal anti-IAP antibodies which can inhibit LRI function when added in solution are competent to activate the respiratory burst when adherent to a surface. KGAGDV peptide and anti-LRI added in solution can inhibit anti-IAP-stimulated respiratory burst. The LRI-IAP-initiated respiratory burst is independent of CD18, as judged by: (a) blockade of inhibition by anti-CD18 mAb with the protein kinase A inhibitor HA1004; (b) enhanced sensitivity of CD18-dependent respiratory burst compared with LRI/IAP-dependent respiratory burst to the tyrosine kinase inhibitors genestein and herbimicin; and (c) generation of a respiratory burst in response to KGAGDV, anti-LRI, and anti-IAP coated surfaces in PMN from a patient with LAD. Despite its apparent CD18 independence, LRI/IAP-initiated respiratory burst requires a solid phase ligand and is sensitive to cytochalasin B. These data suggest a model in which LRI and IAP act together as a single signal transduction unit to activate the phagocyte respiratory burst, in a manner that requires CD18-independent cell adhesion.
Zhou
M
M
Department of Medicine, Washington University, St. Louis, Missouri 63110.
Brown
E J
EJ
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D018821:CD18 Antigens; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism*; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology; D016897:Respiratory Burst; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D016023:Integrins; D008024:Ligands; D008565:Membrane Proteins; D016028:Receptors, Leukocyte-Adhesion; C075596:integrin, leukocyte response; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases