Regulation and lectin activity of the human neutrophil peripheral lymph node homing receptor.
We characterize the nature and regulation of a human neutrophil cell surface antigen recognized by monoclonal antibodies (the DREG series) against a human lymphocyte peripheral lymph node homing receptor. Human neutrophils express high levels of the DREG antigen, whose expression is downregulated after treatment with phorbol myristate acetate, or the chemotactic factors C5a and FMLP. Interestingly, C5a treatment also downregulated the monocyte DREG antigen, but had no effect on expression of the lymphocyte molecule. Within 3 minutes after treatment with C5a, greater than 80% of neutrophil DREG antigen expression is lost, and essentially the molecule is completely removed from the cell surface by 5 minutes. The human neutrophil DREG antigen is 10 Kd larger than the lymphocyte molecule. These features are similar to those of the mouse neutrophil MEL-14 antigen (murine peripheral lymph node homing receptor). The mannose-6-phosphate rich phosphomannan (PPME) binds human lymphocytes via the DREG antigen. PPME also binds neutrophils, but little difference in binding is seen between unactivated and activated cells. We show that PPME binding to unactivated neutrophils is mediated primarily by a cation- and DREG antigen-dependent mechanism, whereas activated neutrophil-PPME binding is DREG antigen- and cation-independent, and may be due to the translocation of lysosomal mannose-6-phosphate receptors to the cell surface. The DREG antibodies offer powerful tools for analyzing the role of homing receptors in human neutrophil-endothelial cell interactions, and also may prove valuable in the clinical assessment of neutrophil activation.
Department of Pathology, Stanford University, CA.
M A
MA
Jutila
T K
TK
Kishimoto
E C
EC
Butcher
D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D037102:Lectins / Q000378:metabolism* / Q000502:physiology; D008214:Lymphocytes / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D008351:Mannans / Q000378:metabolism; D008360:Mannosephosphates / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure*; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D037102:Lectins; D008351:Mannans; D008360:Mannosephosphates; D011971:Receptors, Immunologic; D016201:Receptors, Lymphocyte Homing; C065532:mannose-6-phosphate rich phosphomannan