A Rab11-containing rapidly recycling compartment in macrophages that promotes phagocytosis

Dianne Cox, Donna J. Lee, Benjamin M. Dale, Jero Calafat, Steven Greenberg

Research output: Contribution to journalArticle

172 Citations (Scopus)

Abstract

Macrophages are specialized cells of the immune system that exhibit a prodigious capacity for phagocytosis. The ability of macrophages to internalize a substantial proportion of their plasma membrane during phagocytosis indicates that they possess a mechanism for the rapid renewal of plasma membrane. We examined the role of endocytic membrane recycling in promoting phagocytosis. In contrast to many other cell types, macrophages lack a morphologically distinct peri-centriolar recycling compartment but instead demonstrate an extensive network of transferrin receptor-positive tubules and vesicles that participated in recycling. The rate of transferrin recycling in thioglycollate-elicited murine peritoneal macrophages (thio- macrophages) was exceedingly rapid, with exocytic rate constants that were 2- to 3-fold higher than those of most other cells. Because the GTPase Rab11 has been implicated in transferrin recycling in other cells, we determined its role in transferrin recycling and phagocytosis in macrophages. Macrophages expressing epitope-tagged Rab11 demonstrated the presence of Rab11 in several intracellular membrane compartments, including endosomes and nascent phagosomes. Expression of Rab11 25N, a GTP binding-deficient allele of Rab11, led to a decreased rate of transferrin efflux and impaired Fc(γ)R-mediated phagocytosis, where Fc(γ)R is the receptor for the Fc portion of IgG. In contrast, expression of Rab11 70L, a GTPase-deficient allele of Rab11, led to an increased rate of transferrin efflux and enhanced phagocytosis. We conclude that macrophages have adapted a rapidly mobilizable, endocytic compartment to enhance phagocytosis. Rab11 participates in the recruitment of this compartment to the macrophage cell surface.

Original languageEnglish (US)
Pages (from-to)680-685
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number2
DOIs
StatePublished - Jan 18 2000
Externally publishedYes

Fingerprint

Recycling
Phagocytosis
Macrophages
Transferrin
GTP Phosphohydrolases
Alleles
Cell Membrane
Thioglycolates
Phagosomes
Intracellular Membranes
Transferrin Receptors
Fc Receptors
Endosomes
Peritoneal Macrophages
Guanosine Triphosphate
Epitopes
Immune System
Immunoglobulin G
Membranes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A Rab11-containing rapidly recycling compartment in macrophages that promotes phagocytosis. / Cox, Dianne; Lee, Donna J.; Dale, Benjamin M.; Calafat, Jero; Greenberg, Steven.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 2, 18.01.2000, p. 680-685.

Research output: Contribution to journalArticle

@article{4a9737728b4a4de18c53ad056a122bdd,
title = "A Rab11-containing rapidly recycling compartment in macrophages that promotes phagocytosis",
abstract = "Macrophages are specialized cells of the immune system that exhibit a prodigious capacity for phagocytosis. The ability of macrophages to internalize a substantial proportion of their plasma membrane during phagocytosis indicates that they possess a mechanism for the rapid renewal of plasma membrane. We examined the role of endocytic membrane recycling in promoting phagocytosis. In contrast to many other cell types, macrophages lack a morphologically distinct peri-centriolar recycling compartment but instead demonstrate an extensive network of transferrin receptor-positive tubules and vesicles that participated in recycling. The rate of transferrin recycling in thioglycollate-elicited murine peritoneal macrophages (thio- macrophages) was exceedingly rapid, with exocytic rate constants that were 2- to 3-fold higher than those of most other cells. Because the GTPase Rab11 has been implicated in transferrin recycling in other cells, we determined its role in transferrin recycling and phagocytosis in macrophages. Macrophages expressing epitope-tagged Rab11 demonstrated the presence of Rab11 in several intracellular membrane compartments, including endosomes and nascent phagosomes. Expression of Rab11 25N, a GTP binding-deficient allele of Rab11, led to a decreased rate of transferrin efflux and impaired Fc(γ)R-mediated phagocytosis, where Fc(γ)R is the receptor for the Fc portion of IgG. In contrast, expression of Rab11 70L, a GTPase-deficient allele of Rab11, led to an increased rate of transferrin efflux and enhanced phagocytosis. We conclude that macrophages have adapted a rapidly mobilizable, endocytic compartment to enhance phagocytosis. Rab11 participates in the recruitment of this compartment to the macrophage cell surface.",
author = "Dianne Cox and Lee, {Donna J.} and Dale, {Benjamin M.} and Jero Calafat and Steven Greenberg",
year = "2000",
month = "1",
day = "18",
doi = "10.1073/pnas.97.2.680",
language = "English (US)",
volume = "97",
pages = "680--685",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "2",

}

TY - JOUR

T1 - A Rab11-containing rapidly recycling compartment in macrophages that promotes phagocytosis

AU - Cox, Dianne

AU - Lee, Donna J.

AU - Dale, Benjamin M.

AU - Calafat, Jero

AU - Greenberg, Steven

PY - 2000/1/18

Y1 - 2000/1/18

N2 - Macrophages are specialized cells of the immune system that exhibit a prodigious capacity for phagocytosis. The ability of macrophages to internalize a substantial proportion of their plasma membrane during phagocytosis indicates that they possess a mechanism for the rapid renewal of plasma membrane. We examined the role of endocytic membrane recycling in promoting phagocytosis. In contrast to many other cell types, macrophages lack a morphologically distinct peri-centriolar recycling compartment but instead demonstrate an extensive network of transferrin receptor-positive tubules and vesicles that participated in recycling. The rate of transferrin recycling in thioglycollate-elicited murine peritoneal macrophages (thio- macrophages) was exceedingly rapid, with exocytic rate constants that were 2- to 3-fold higher than those of most other cells. Because the GTPase Rab11 has been implicated in transferrin recycling in other cells, we determined its role in transferrin recycling and phagocytosis in macrophages. Macrophages expressing epitope-tagged Rab11 demonstrated the presence of Rab11 in several intracellular membrane compartments, including endosomes and nascent phagosomes. Expression of Rab11 25N, a GTP binding-deficient allele of Rab11, led to a decreased rate of transferrin efflux and impaired Fc(γ)R-mediated phagocytosis, where Fc(γ)R is the receptor for the Fc portion of IgG. In contrast, expression of Rab11 70L, a GTPase-deficient allele of Rab11, led to an increased rate of transferrin efflux and enhanced phagocytosis. We conclude that macrophages have adapted a rapidly mobilizable, endocytic compartment to enhance phagocytosis. Rab11 participates in the recruitment of this compartment to the macrophage cell surface.

AB - Macrophages are specialized cells of the immune system that exhibit a prodigious capacity for phagocytosis. The ability of macrophages to internalize a substantial proportion of their plasma membrane during phagocytosis indicates that they possess a mechanism for the rapid renewal of plasma membrane. We examined the role of endocytic membrane recycling in promoting phagocytosis. In contrast to many other cell types, macrophages lack a morphologically distinct peri-centriolar recycling compartment but instead demonstrate an extensive network of transferrin receptor-positive tubules and vesicles that participated in recycling. The rate of transferrin recycling in thioglycollate-elicited murine peritoneal macrophages (thio- macrophages) was exceedingly rapid, with exocytic rate constants that were 2- to 3-fold higher than those of most other cells. Because the GTPase Rab11 has been implicated in transferrin recycling in other cells, we determined its role in transferrin recycling and phagocytosis in macrophages. Macrophages expressing epitope-tagged Rab11 demonstrated the presence of Rab11 in several intracellular membrane compartments, including endosomes and nascent phagosomes. Expression of Rab11 25N, a GTP binding-deficient allele of Rab11, led to a decreased rate of transferrin efflux and impaired Fc(γ)R-mediated phagocytosis, where Fc(γ)R is the receptor for the Fc portion of IgG. In contrast, expression of Rab11 70L, a GTPase-deficient allele of Rab11, led to an increased rate of transferrin efflux and enhanced phagocytosis. We conclude that macrophages have adapted a rapidly mobilizable, endocytic compartment to enhance phagocytosis. Rab11 participates in the recruitment of this compartment to the macrophage cell surface.

UR - http://www.scopus.com/inward/record.url?scp=0034681147&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034681147&partnerID=8YFLogxK

U2 - 10.1073/pnas.97.2.680

DO - 10.1073/pnas.97.2.680

M3 - Article

VL - 97

SP - 680

EP - 685

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 2

ER -