Role of complements C3 and C5 in the phagocytosis of liposomes by human neutrophils.
During the course of a previous investigation, we noticed that the uptake of liposomes by human polymorphonuclear neutrophils (PMNs) was significantly lower in the presence of heat-inactivated serum compared to that in intact whole serum (Scieszka et al., Pharm. Res. 5:352, 1988). This observation suggested the participation of heat-labile complement components in the phagocytic process. In this report we conclude that complement C3bi is the component responsible for opsonization of the liposome surface. Phagocytosis was not supported by C3-deficient serum, and phagocytosis in whole serum was blocked by the antibody to the receptor for C3bi (CR3) but not by the antibody to the receptor for C3b (CR1). We also found that with C5-deficient serum the level of uptake was minimal but slightly higher than without any serum. When exogenous C5a was added along with C5-deficient serum, uptake levels similar in magnitude to those observed with intact serum were obtained. We conclude that C5a enhances phagocytosis of opsonized liposomes by activating the phagocytic capacity of CR3 on the PMN.
Scieszka
J F
JF
Drug Delivery Systems Research, Upjohn Company, Kalamazoo, Michigan 49001.
Maggiora
L L
LL
Wright
S D
SD
Cho
M J
MJ
D000293:Adolescent; D000328:Adult; D003176:Complement C3 / Q000502:physiology*; D003179:Complement C3b / Q000502:physiology; D003182:Complement C5 / Q000502:physiology*; D015936:Complement C5a / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology*; D009895:Opsonin Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology*; D011951:Receptors, Complement / Q000378:metabolism; D017463:Receptors, Complement 3b
D003176:Complement C3; D003182:Complement C5; D008081:Liposomes; D009895:Opsonin Proteins; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D003179:Complement C3b; D015936:Complement C5a