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2018 ; 8
(1
): 11253
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Quantitative Profiling of the Lymph Node Clearance Capacity
#MMPMID30050160
Clement CC
; Wang W
; Dzieciatkowska M
; Cortese M
; Hansen KC
; Becerra A
; Thangaswamy S
; Nizamutdinova I
; Moon JY
; Stern LJ
; Gashev AA
; Zawieja D
; Santambrogio L
Sci Rep
2018[Jul]; 8
(1
): 11253
PMID30050160
show ga
Transport of tissue-derived lymphatic fluid and clearance by draining lymph nodes
are pivotal for maintenance of fluid homeostasis in the body and for
immune-surveillance of the self- and non-self-proteomes. Yet a quantitative
analysis of nodal filtration of the tissue-derived proteome present in lymphatic
fluid has not been reported. Here we quantified the efficiency of nodal clearance
of the composite proteomic load using label-free and isotope-labeling proteomic
analysis of pre-nodal and post-nodal samples collected by direct cannulation.
These results were extended by quantitation of the filtration efficiency of
fluorophore-labeled proteins, bacteria, and beads infused at physiological flow
rates into pre-nodal lymphatic collectors and collected by post-nodal
cannulation. We developed a linear model of nodal filtration efficiency dependent
on pre-nodal protein concentrations and molecular weight, and uncovered criteria
for disposing the proteome incoming from defined anatomical districts under
physiological conditions. These findings are pivotal to understanding the maximal
antigenic load sustainable by a draining node, and promote understanding of
pathogen spreading and nodal filtration of tumor metastasis, potentially helping
to improve design of vaccination protocols, immunization strategies and drug
delivery.