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Intravital Microscopy of the Spleen: Quantitative Analysis of Parasite Mobility and Blood Flow
Published on: January 14, 2012
Lymphocyte migration in the spleen: the effect of macrophage elimination
G Kraal1, H Rodrigues, K Hoeben
1Department of Cell Biology and Immunology, Free University, Amsterdam, The Netherlands.
Abstract:
To study the influence of macrophages on the migration and distribution of lymphocytes in the spleen, macrophages were eliminated from the spleen of mice by injection of liposomes in which DMDP was encapsulated. This leads to an elimination of macrophages in both the red pulp and marginal zone of the spleen within 1-2 days. In these animals the distribution of lymphocytes was determined by transfer of either syngeneic fluoresceinated or Ly 5 congeneic cells. It was found that after elimination of the macrophages the number of lymphocytes immigrating into the spleen had decreased, although a comparable mode of compartimentalization was found with an initial localization in the marginal zone and a subsequent distribution into the white pulp. After this elimination spleen macrophage subsets return with different kinetics, and in this way the influence of the red pulp macrophages, the marginal zone macrophages and the marginal metallophilic macrophages on lymphocyte immigration and redistribution could be investigated. A quantitative decrease of immigration was still found when red pulp and marginal metallophilic macrophages had repopulated their compartments, but was only fully restored when the last population to repopulate the spleen after treatment with DMDP-liposomes, the marginal zone macrophages, had returned. Experiments with isolated T and B cells showed that the elimination of macrophages had a profound effect on the localization of B cells in the white pulp, whereas it hardly affected T cells.
Insights
Macrophages are crucial for lymphocyte distribution in the spleen. Their elimination significantly reduced lymphocyte immigration, particularly affecting B cell localization in the white pulp.
Area of Science:
- Immunology
- Cell Biology
- Spleen Microenvironment
Background:
- Macrophages play a vital role in immune responses within the spleen.
- Understanding macrophage subsets and their specific functions in lymphocyte trafficking is essential.
Purpose of the Study:
- To investigate the influence of splenic macrophages on lymphocyte migration and distribution.
- To elucidate the distinct roles of red pulp, marginal zone, and marginal metallophilic macrophages in lymphocyte homing.
Main Methods:
- Selective elimination of splenic macrophages using DMDP-encapsulated liposomes in mice.
- Tracking of transferred syngeneic fluoresceinated or Ly 5 congeneic lymphocytes.
- Analysis of lymphocyte distribution and repopulation kinetics of macrophage subsets.
Main Results:
- Macrophage elimination led to a quantitative decrease in lymphocyte immigration into the spleen.
- Lymphocyte compartmentalization initially occurred in the marginal zone, followed by white pulp distribution, even after macrophage depletion.
- Different splenic macrophage subsets repopulated at distinct rates, impacting lymphocyte immigration restoration.
- B cell localization in the white pulp was profoundly affected, while T cell localization remained largely unchanged.
Conclusions:
- Splenic macrophages, particularly marginal zone macrophages, are critical for the full restoration of lymphocyte immigration.
- Distinct macrophage populations exert specific influences on lymphocyte trafficking and distribution within the spleen.
- Macrophage depletion differentially impacts T and B cell localization, highlighting subset-specific interactions.
