Increased expression of complement decay-accelerating factor during activation of human neutrophils.
Decay-accelerating factor (DAF) is a membrane protein that protects blood cells from damage by autologous complement. Using monoclonal antibodies in both direct-binding studies and flow cytometry, we found that resting neutrophils (polymorphonuclear leukocytes [PMN]) expressed 10(4) DAF molecules on their surface, and that surface DAF expression more than doubled when the cells were activated. Upregulation of surface DAF occurred within minutes, paralleled the upregulation of complement receptor types 1 and 3 (CR1 and CR3), and was not dependent on new protein synthesis. It was unaffected by EDTA but was inhibited by 10 microM trifluoperazine, suggesting involvement of intracellular Ca2+ and calmodulin or protein kinase C. Upon activation, the affected PMN lacking surface DAF from patients with paroxysmal nocturnal hemoglobulinuria failed to increase DAF expression. In contrast, these cells increased CR1 and CR3 expression normally, suggesting that DAF deficiency in affected cells involves abnormal synthesis or packaging of DAF for intracellular storage. Translocation of DAF to the cell surface induced by chemoattractants may be important in allowing PMN to survive and function at inflammatory sites where there is rapid complement turnover.
D018958:CD55 Antigens; D002118:Calcium / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D002630:Chemotactic Factors / Q000494:pharmacology; D003167:Complement Activation; D003169:Complement Inactivator Proteins / Q000378:metabolism*; D004987:Ethers / Q000494:pharmacology; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood*; D015759:Ionomycin; D008565:Membrane Proteins / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology*; D013696:Temperature; D014268:Trifluoperazine / Q000494:pharmacology
D018958:CD55 Antigens; D002630:Chemotactic Factors; D003169:Complement Inactivator Proteins; D004987:Ethers; D008565:Membrane Proteins; D014268:Trifluoperazine; D015759:Ionomycin; D002118:Calcium