Complement Receptor 3 (CD11b/CD18) Mediates Type I and Type II Phagocytosis During Nonopsonic and Opsonic Phagocytosis, Respectively

TLDR

Two types of opsonic phagocytosis are defined by receptor engagement: FcγRs mediate type I phagocytosis of IgG‑coated particles, while complement receptor 3 (CR3) mediates type II phagocytosis of complement‑coated particles and also mediates nonopsonic phagocytosis of zymosan and Mycobacterium kansasii via distinct sites. Using Chinese hamster ovary cells stably expressing human CR3, the authors compared CR3‑mediated ingestion of nonopsonized zymosan and Mycobacterium kansasii with opsonized zymosan. CR3‑mediated phagocytosis of nonopsonized zymosan and Mycobacterium kansasii depends on Rac and Cdc42 but not Rho, requires Src family kinase Hck activity, whereas opsonized zymosan is internalized independently of these factors; thus CR3 mediates type I phagocytosis under nonopsonic conditions and type II under opsonic conditions, providing first evidence that a single receptor can mediate both types depending on ligand.

Abstract

Abstract Two types of opsonic phagocytosis have been defined depending on the receptor engaged: FcγRs mediate type I phagocytosis of IgG-coated particles; complement receptor 3 (CR3) mediates type II phagocytosis of complement-coated particles. In addition to opsonic phagocytosis, CR3 also mediates nonopsonic phagocytosis of zymosan (Z) and Mycobacterium kansasii through engagement of distinct sites. Using Chinese hamster ovary cells stably expressing human CR3, we studied CR3-mediated ingestion of nonopsonized particles, Z or M. kansasii, compared with opsonized zymosan (OZ). We show that 1) while OZ sinks into cells, Z is engulfed by pseudopodia as visualized by electron microscopy; 2) in contrast to OZ, nonopsonic phagocytosis of Z and M. kansasii depends on Rac and Cdc42 but not on Rho activity; and 3) CR3-mediated phagocytosis of Z depends on the kinase activity of the Src family tyrosine kinase Hck, while OZ internalization does not. Therefore, CR3 mediates type I phagocytosis under nonopsonic conditions and type II under opsonic conditions. This is the first evidence that a single receptor can mediate both types of phagocytosis depending on the ligand used.