Anti-Mac-1 selectively inhibits the mouse and human type three complement receptor.

Abstract

Monoclonal antibodies (MAb) 1 have proven to be of great value in identifying the cellular lineages and subsets that give rise to the diversity of the immune system. Recently, interest has focused on the use of such antibodies to evaluate macrophage heterogeneity (1-5), and these reagents have added measurably to the information attained using heterospecific antisera (6). The first and perhaps best characterized of these antibodies, the rat anti-mouse M1/70 (anti-Mac-i) MAb, defines an antigen containing two polypeptides of 170,000 and 95,000 mol wt found on the surface of mouse macrophages, polymorphonuclear leukocytes (PMNL), and natural killer cells (1, 2, 7). The M1/70 MAb cross-reacts with human cells. Mac-1 has the same distribution in humans as in the mouse (8). To date, no function has been attributed to this antigen. The difficulty in ascribing function to antibody-defined cell surface structures has been a characteristic of studies on differentiation and cell type-specific antigens.Current evidence indicates that cells of the myeloid lineage (mononuclear phagocytes and PMNL) bear two distinct cell surface receptors for fragments of activated C3 (9-12, and reviewed in 13). The type one complement receptor (CR1) displays specificity for C3b and C4b (14-17). This receptor has been isolated and consists of a single polypeptide chain of 205,000 tool wt (14, 15). The type three complement receptor (CR3) interacts with C3b inactivator cleaved C3b (C3bi) and further degradation products of C3bi termed a2D or C3d,g (16-22). To date, no information is available concerning the structure of CR3. The type two complement receptor (CRz), which interacts with C3d, is carried on lymphocytes but not on mononuclear phagocytes or PMNL (13, 23).The purpose of this report is to present evidence that the anti-Mac-1 MAb selectively blocks the rosetting of C3bi-coated erythrocytes to murine macrophages and human PMNL. These results suggest that the Mac-1 antigen is intimately associated with or actually represents the type three complement receptor on these *

The integrin αMβ2 anchors hematopoietic progenitors in the bone marrow during enforced mobilization

“…on April 7, 2019. by guest www.bloodjournal.org From Although ␣M␤2 was initially discovered as a macrophage complement receptor, 10 it ranks among the most pleiotropic cell surface adhesion molecules that can mediate interactions with platelets, 39 coagulation proteins, 40,41 complement components, 10 proteolytic enzymes, 11 carbohydrates, 15 and cellular receptors. 14 The interactions described here between ␣M␤2 expressed on myeloid cells and soluble or immobilized fucoidan are consistent with the recent work of Zen et al 17 who showed a direct binding between fucoidan and purified immobilized ␣M␤2.…”

“…8,9 ␣M␤2 displays highly promiscuous interactions with cellular and extracellular matrix ligands such as intercellular adhesion molecule-1 (ICAM-1) and -2, fibrinogen, iC3b, elastase, sulfated carbohydrates, zymosan, urokinase plasminogen activator, and ␤-glucan. [10][11][12][13][14][15][16][17] In the context of transendothelial migration, ␣M␤2 binds ICAM-1 expressed on activated endothelium and mediates the arrest and diapedesis of leukocytes. 18 Like most other integrins, the affinity of ␣M␤2 for ligands dramatically increases after activation by various stimuli, and its avidity is increased by the translocation to the cell surface of granular stores, a process that parallels the shedding of L-selectin from the surface of neutrophils.…”

Local opsonization by secreted macrophage complement components. Role of receptors for complement in uptake of zymosan.

“…The M~ CR3 was implicated by the use of two independent monoclonal ab. M1/70 specifically prevents binding to mouse M~ of iC3b-coated but not C3b-coated erythrocytes or EIgG (15) and inhibits immune enhancement of flavivirus replication mediated by complement, but not IgG (43). MO1 immunoprecipitates the human analogue of Mac-1 and also blocks binding of EiC3b rosettes to normal human monocytes (16).…”

Expression of a structural domain of the β2 subunit essential for αMβ2 ligand recognition

“…␣ M ␤ 2 , whose expression is restricted predominantly to myeloid and natural killer cells, is involved in a variety of interactions including phagocytosis of opsonized particles [9], adherence to endothelium [10,11], neutrophil homotypic aggregation, and chemotaxis [12]. ␣ M ␤ 2 recognizes a multiplicity of protein ligands including the complement C3 fragment iC3b [9,13], ICAM-1 [14], and the coagulation proteins fibrinogen [15] and Factor X [16].…”