Differential effects of anti-rat CD11b monoclonal antibodies on granulocyte adhesiveness.
Four different monoclonal antibodies (mAbs) reactive with rat CD11b (ED7, ED8, OX-42 and 1B6c) have been characterized for their ability to induce homotypic aggregation of granulocytes or to modify granulocyte adhesiveness triggered by phorbol myristate acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP). Cross-blocking experiments showed that these mAbs recognize at least three different epitopes on CD11b. OX-42 mAb recognizes an inhibitory epitope since the mAb inhibited homotypic aggregation of granulocytes and their adherence to plastic in the presence of PMA or fMLP. ED7 and ED8 induced homotypic aggregation of granulocytes which was blocked by OX-42 and anti-CD18 mAb (WT3) suggesting that CR3 itself is involved in the adhesion process. The aggregation was dependent on active cell metabolism, intact cytoskeleton, divalent cations and activation of tyrosine kinases sensitive to genistein. Staurosporine, okadaic acid and orthovanadate potentiated the aggregation. ED7 and ED8 potentiated homotypic aggregation and adhesion of granulocytes to plastic caused by fMLP, but inhibited granulocyte adhesion to plastic induced by PMA. 1B6c recognizes an epitope that transmits a proaggregatory signal upon binding of the mAb but only if the granulocytes are in contact with plastic or are activated by fMLP. In contrast, 1B6c inhibited granulocyte adhesion to plastic triggered by PMA or fMLP. These data suggest the existence of functionally different epitopes on rat CD11b and indicate that some anti-CD11b mAbs are able to functionally activate CR3.
Drasković-Pavlović
B
B
Institute of Medical Research, Military Medical Academy, Belgrade, Yugoslavia.
Van Der Laan
L J
LJ
Pejnović
N
N
Dijkstra
C D
CD
Colić
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002448:Cell Adhesion / Q000276:immunology; D002449:Cell Aggregation / Q000276:immunology; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D051381:Rats; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D000939:Epitopes; D016177:Macrophage-1 Antigen