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Are murine marginal zone macrophages the splenic white pulp analog of high endothelial venules?

journal contribution
posted on 2023-05-16, 09:50 authored by Alan Lyons, Parish, CR
The entry of lymphocytes into the spleen, in contrast to lymph nodes, does not involve high endothelial venule (HEV) interaction. The precise point of entry, as well as the mechanism by which lymphocytes enter the lymphoid areas of the spleen, remains controversial. We examined in detail the effect of two agents, pertussis toxin (PT) and the sulfated polysaccharide fucoidan, on splenic lymphocyte entry and positioning. These have previously been shown to interfere with lymphocyte extravasation across HEV. PT prevents lymphocyte extravasation, but not binding, to HEV, whereas fucoidan prevents binding and thus subsequent extravasation. Studies presented here show that pretreatment of murine lymphocytes with PT does not numerically affect entry into spleen, but profoundly alters lymphocyte positioning within the spleen. When fluorescently labeled, PT-treated lymphocytes are injected intravenously, they initially accumulate in the marginal zone, in apparent association with the layer of marginal zone macrophages (MZM∅) which form a shell around the white pulp. They fail to traverse this layer into the white pulp, and subsequently localize in the red pulp. In contrast, untreated cells initially appear in the marginal zone, then continue to migrate into the white pulp after traversing the MZM∅ layer. The localization of PT-pretreated lymphocytes adjacent to the MZM∅ layer is disrupted by intravenous administration of fucoidan. Using a flow cytometric assay of aggregation between MZM∅ and lymphocytes, we confirmed that fucoidan is also able to inhibit this association in vitro, whereas PT has no effect on this interaction. We propose that MZM∅ in the mouse are the splenic analog of HEV, forming the port of entry of lymphocytes into the white pulp of the spleen.

History

Publication title

European Journal of Immunology

Volume

25

Issue

11

Pagination

3165-3172

ISSN

0014-2980

Department/School

Tasmanian School of Medicine

Publisher

Wiley-V C H Verlag Gmbh

Place of publication

The Netherlands

Repository Status

  • Restricted

Socio-economic Objectives

Expanding knowledge in the environmental sciences

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