Activation of the neutrophil respiratory burst by chemoattractants: regulation of the N-formyl peptide receptor in the plasma membrane.
The N-formyl peptide receptor mediates a number of host defensive responses of human neutrophils that result in chemotaxis, secretion of hydrolytic enzymes, and superoxide generation. Inappropriate activation or defective regulation of these responses can result in pathogenic states responsible for inflammatory disease. The receptor is a 50 to 70-kD, integral plasma membrane glycoprotein with intracellular and surface localization. Its abundance in the membrane is regulated by membrane flow and recycling processes. Cytoskeletal interactions are believed to control its organization in the plane of the membrane and interaction with other proteins. The receptor's most important interaction is with guanyl nucleotide binding proteins that serve as signal transduction partners ultimately leading to activation of effector responses. Because the interaction of the receptor with G proteins is necessary for transduction, control of this interaction may be at the root of understanding the molecular control of responses in these cells. This review briefly summarizes some of the molecular properties, dynamics, and interactions of this receptor system in human neutrophils and discusses how these characteristics may pertain to the activation and control of superoxide generation.
Jesaitis
A J
AJ
Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, California 92037.
Allen
R A
RA
D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000502:physiology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000378:metabolism*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction; D013481:Superoxides / Q000097:blood*
D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C022709:superoxide-forming enzyme