The molecular biology of leukocyte chemoattractant receptors.
Leukocytes migrate from the blood to sites of inflammation in response to locally produced chemoattractants that activate specific cell surface receptors. The primary structures of leukocyte receptors for N-formyl peptides, C5a, platelet-activating factor, and 8 of the 18 known human chemokines (interleukin-8 and related molecules) have been deduced from cloned cDNAs. All of these are seven-transmembrane-domain rhodopsin-like G protein-coupled receptors. Biochemical and molecular genetic analysis of the chemoattractant receptors indicates that the chemoattractants may have both broadly overlapping as well as specialized roles in the regulation of acute and chronic inflammation. Interestingly, the chemokine receptors have functional homologues in human cytomegalovirus and Herpesvirus saimiri. Moreover, the Duffy antigen, which mediates invasion of erythrocytes by Plasmodium vivax, a major cause of malaria, is also a chemokine binding protein. These surprising developments suggest that in addition to leukocyte-mediated inflammation, the chemokines may also be involved in erythrocyte function and, through molecular mimicry, in microbial pathogenesis.
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
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Murphy
D000595:Amino Acid Sequence; D000818:Animals; D002630:Chemotactic Factors / Q000378:metabolism / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D004375:Duffy Blood-Group System / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000502:physiology*; D018121:Receptors, Cytokine / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology
D002630:Chemotactic Factors; D004375:Duffy Blood-Group System; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D019204:GTP-Binding Proteins