v-SNARE-dependent secretion is required for phagocytosis

v-SNARE-dependent secretion is required for phagocytosis

^*Division of Cell Biology, Hospital for Sick Children, Toronto, Ontario, M5G 1X8 Canada; ^†Department of Surgery, The Toronto Hospital, Toronto, Ontario, M5G 2C4 Canada; and ^‡Department of Medicine, University of Pennsylvania, Philadelphia, PA 10104-4283

Edited by William E. Paul, National Institutes of Health, Bethesda, MD, and approved August 14, 1998 (received for review March 6, 1998)

Abstract

Phagosomes are generally believed to form by gradual apposition of the plasma membrane of leukocytes onto the surface of invading microorganisms. The internalization of the encapsulated particle is therefore predicted to reduce the surface area of the phagocyte. Contrary to this prediction, we observed that phagocytosis is associated with a net increase in cell surface area, suggesting the concomitant occurrence of exocytosis. Selective cleavage of components of the secretory machinery by microinjection or transfection of bacterial neurotoxins induced a pronounced inhibition of phagocytosis. These observations indicate that vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptor-mediated exocytosis of endomembranes is essential for optimal completion of particle internalization during phagocytosis.

Footnotes

↵ § To whom reprint requests should be addressed at: Division of Cell Biology, Hospital for Sick Children, 555 University Ave., Toronto, Ontario, M5G 1X8 Canada. e-mail: sga{at}sickkids.on.ca.
This paper was submitted directly (Track II) to the Proceedings Office.
ABBREVIATIONS:

VAMP-2,

vesicle-associated membrane protein 2;

NSF,

N-ethylmaleimide-sensitive factor;

SNARE,

soluble NSF attachment protein (SNAP) receptor;

v-SNARE,

vesicle SNARE;

TeTx-LC,

tetanus toxin light chain;

SRBC,

sheep red blood cell;

OPZ,

opsonized zymosan;

CHO,

Chinese hamster ovary;

GFP,

green fluorescence protein;

FITC,

fluorescein isothiocyanate