title: The roles of complement receptors type 1 (CR1, CD35) and type 3 (CR3, CD11b/CD18) in the regulation of the immune complex-elicited respiratory burst of polymorphonuclear leukocytes in whole blood.
abstract: The binding of immune complexes (IC) to polymorphonuclear leukocytes (PMN) and the consequent respiratory burst (RB) were investigated in whole blood cell preparations suspended in 75% human serum, using flow cytometry. Blockade of the complement receptor (CR)1 receptor sites for C3b on whole blood cells using the monoclonal antibody (mAb) 3D9 resulted in a 1.9-fold increase in the IC-elicited PMN RB after 5 min of incubation, rising to 3.1-fold after 40 min. This enhancement was not due to increased IC deposition on PMN. Blockade of CR3 abrogated the mAb 3D9-induced rise in RB activity and inhibited the IC binding to PMN in a whole blood cell preparation, with or without mAb 3D9, by approximately 40% from 15-40 min while reducing their RB over 40 min to approximately one third. Blockade of CR1 on either erythrocytes (E) or leukocytes, before mixing the populations, revealed that the potentiation of the RB by mAb 3D9 was associated with abrogation of E-CR1 function, whereas blockade of leukocyte-CR1 had a diminishing effect. Exposure to IC at high concentrations induced release of both specific and azurophilic granule contents from PMN. The latter was CR3 dependent in that blockade of the receptor inhibited the lactoferrin release by one third during 40 min of incubation. In conclusion, CR3 plays a significant role in the IC-mediated generation of an RB and release of specific granules by PMN, while CR1 on whole blood cells, primarily E CR1, restricts the IC-elicited RB in PMN. We propose that CR1 in whole blood promotes the degradation of IC-bound iC3b to C3dg, thereby rendering the IC inaccessible for binding to CR3.
authors.affiliation: Institute of Medical Biology, Odense University, Denmark.
authors.forename: C H
authors.initials: CH
authors.lastname: Nielsen
authors.forename: S
authors.initials: S
authors.lastname: Antonsen
authors.forename: S H
authors.initials: SH
authors.lastname: Matthiesen
authors.forename: R G
authors.initials: RG
authors.lastname: Leslie
mesh_terms: D000936:Antigen-Antibody Complex / Q000097:blood / Q000502:physiology*; D018821:CD18 Antigens / Q000097:blood / Q000502:physiology*; D015550:Cell Degranulation / Q000276:immunology; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology; D006801:Humans; D016177:Macrophage-1 Antigen / Q000097:blood / Q000502:physiology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D017463:Receptors, Complement 3b / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D016897:Respiratory Burst / Q000276:immunology*
chemical_list: D000936:Antigen-Antibody Complex; D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D017463:Receptors, Complement 3b