Active macromolecule uptake by lymph node antigen-presenting cells: a novel mechanism in determining sentinel lymph node status.
BACKGROUND
Although sentinel lymph node (SLN) biopsy is a powerful staging tool for patients with melanoma and breast cancer, controversy remains regarding specific aspects of technique. We examined particle uptake by antigen-presenting cells (APCs) to determine if this mechanism is responsible for the differential retention of radioactivity in SLNs relative to nonsentinel lymph nodes (NSLNs).


METHODS
Mapping was conducted in pigs injected with vital blue dye, fluoroscein isothiocyanate-labeled human serum albumin (FITC-HSA), and one of two 99mtechnetium-labeled tracers, i.e., human serum albumin, a small macromolecule, or unfiltered sulfur colloid, a mixture of small and large particles. Macromolecule uptake by APCs was studied in vitro by using FITC-HSA and measured by fluorescence-activated cell sorting (FACS). SLNs and NSLNs were analyzed by fluorescence microscopy or FACS, with counterstaining for leukocyte cell surface markers.


RESULTS
Both radiotracers were effective. Cultured APCs rapidly took up FITC-HSA. Microscopy showed FITC-HSA in the subcapsular sinus of SLNs shortly after injection and subsequent distribution to interfollicular areas. FACS revealed increasing amounts of FITC-HSA in SLNs over time. Cells responsible for uptake were APCs, expressing major histocompatibility (locus) class II.


CONCLUSIONS
This report establishes active macromolecule uptake as a mechanism that determines SLN status. This mechanism has important implications for performing SLN biopsy.
Faries
M B
MB
Department of Surgery, University of Pennsylvania, Philadelphia, USA.
Bedrosian
I
I
Reynolds
C
C
Nguyen
H Q
HQ
Alavi
A
A
Czerniecki
B J
BJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D008198:Lymph Nodes / Q000166:cytology* / Q000000981:diagnostic imaging* / Q000276:immunology; D046911:Macromolecular Substances; D010316:Particle Size; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D013552:Swine; D013668:Technetium Tc 99m Aggregated Albumin / Q000008:administration & dosage; D013671:Technetium Tc 99m Sulfur Colloid / Q000627:therapeutic use*
D046911:Macromolecular Substances; D019275:Radiopharmaceuticals; D013668:Technetium Tc 99m Aggregated Albumin; D013671:Technetium Tc 99m Sulfur Colloid